Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.

Genotyping, sequencing and analysis of 140,000 adults from Mexico City.

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Effectiveness of no drainage after elective day-case laparoscopic cholecystectomy, even with intraoperative gallbladder perforation: a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) has been carried out as day-case surgery. Current guidelines do not mention the role of drainage after LC. In particular, data stay blank with no prospective study on drainage management when gallbladder perforation (GP) accidentally occurs intraoperatively. METHODS: A randomized controlled trial was conducted to compare clinical outcomes of drainage and no drainage after elective day-case LC. Intraoperative GP was recorded. The primary and secondary outcomes were major and minor complications, respectively. RESULTS: Two hundred patients were randomized. No major complications occurred in either group. In secondary outcomes, nausea/vomiting, pain, hospital stay, and cost were similar in the drainage group and no drainage group; postoperative fever, WBC, and CRP levels were significantly lower in the no drainage group. GP occurred in 32 patients. Male patients with higher BMI and CRP and abdominal pain within 1 month were more likely to occur GP. Subgroup analysis of GP, primary outcomes, and most secondary outcomes had no difference. Postoperative WBC and CRP were higher in the drainage group. Postoperative fever occurred in 63 patients. Univariate analysis of fever showed that blood loss, drainage, postoperative WBC, CRP, and hospital stay were significant. Multivariable logistic regression analysis demonstrated that drainage was an independent risk factor for fever after LC (OR 3.418, 95% CI 1.392-8.390; p = 0.007). CONCLUSIONS: No drainage after elective day-case LC is safe and associated with fewer complications, even in intraoperative GP. The trial proves that drainage is an independent risk factor for postoperative fever. The use of a drain after LC may lead to an unsuccessful day-case procedure by causing fever, elevated CRP, and extended hospital stay (NCT03909360).

Hem-o-lok clip migration to the common bile duct after laparoscopic common bile duct exploration: A case report.

BACKGROUND: Laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) has been widely used for management of gallbladder and common bile duct (CBD) stones. Post-operative clip migration is a rare complication of laparoscopic biliary surgery, which can serve as a nidus for stone formation and cause recurrent cholangitis. CASE SUMMARY: A 59-year-old female was admitted to hospital because of fever and acute right upper abdominal pain. She has a history of LC and had a LCBDE surgery 2 mo ago. Physical examination revealed tenderness in the upper quadrant of right abdomen. Computed tomography scan demonstrated a high-density shadow at the distal CBD, which was considered as migrated clips. The speculation was confirmed by endoscopic retrograde cholangiopancreatography examination, and two displaced Hem-o-lok clips were removed with a stone basket. No fever or abdominal pain presented after the operation. In addition to the case report, literature regarding surgical clip migration after laparoscopic biliary surgery was reviewed and discussed. CONCLUSION: Incidence of postoperative clip migration may be reduced by using clips properly and correctly; however, new methods should be explored to occlude cystic duct and vessels. If a patient with a past history of LC or LCBDE presents with features of sepsis and recurrent upper quadrant pain, clip migration must be considered as one of the differential diagnosis.

MiR-135b-5p is an oncogene in pancreatic cancer to regulate GPRC5A expression by targeting transcription factor KLF4.

KLF4 is implicated in tumor progression of pancreatic cancer, but the molecular regulatory mechanism of KLF4 needs to be further specified. We aimed to probe molecular regulatory mechanism of KLF4 in malignant progression of pancreatic cancer. qRT-PCR or western blot was completed to test levels of predicted genes. Dual-luciferase and chromatin immunoprecipitation (ChIP) assays were designed to validate binding between genes. Cell viability and oncogenicity detection were used for in vitro and vivo functional assessment. KLF4 was a downstream target of miR-135b-5p. KLF4 could regulate GPRC5A level. MiR-135b-5p was notably increased in cancer cells, and overexpressing KLF4 functioned a tumor repressive role, which could be restored by miR-135b-5p. Besides, cell malignant phenotypes could be inhibited through reducing miR-135b-5p level, but they were restored by GPRC5A. Our results stressed that KLF4, as a vital target of miR-135b-5p, could influence promoter region of GPRC5A, thus affecting the malignant progression of pancreatic cancer.

Treatment of microvascular invasion in hepatocellular carcinoma with drug-loaded nanocomposite platform under synergistic effect of magnetic field/near-infrared light.

Despite progress in clinical treatment, microvascular invasion (MVI) remains a major factor for frequent recurrence and metastasis of hepatocellular carcinoma (HCC) after liver resection and surgery. Thus, this study constructed a target nanoplatform (αCD97-USPIO-Au-DDP) with magnetic field/near-infrared (NIR) light response using ultrasmall superparamagnetic iron oxide-gold nanoporous spheres (USPIO-Au) as multifunctional nanocarrier. Anticancer drug cisplatin (DDP) was loaded, and specifically expressed CD97 protein in MVI was taken as the therapeutic target. The αCD97-USPIO-Au-DDP showed favorable photothermal and stable properties under the NIR light at 808 nm wavelength. As suggested by in vitro and in vivo research, this composite nanopreparation could effectively reduce damage to normal organs and showed good biocompatibility. Excellent magnetic targeting function of nanocarrier and modification of αCD97 strengthened accumulation of composite nanodrug in tumor to inhibit tumor growth. This system may have important ramifications for treatment of MVI in HCC.

Exome sequencing and analysis of 454,787 UK Biobank participants.

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10-11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.

Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids.

BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.

Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank.

The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a private-public partnership between the UK Biobank (UKB) and eight biopharmaceutical companies that will complete the sequencing of exomes for all ~500,000 UKB participants. Here, we describe the early results from ~200,000 UKB participants and the features of this project that enabled its success. The biopharmaceutical industry has increasingly used human genetics to improve success in drug discovery. Recognizing the need for large-scale human genetics data, as well as the unique value of the data access and contribution terms of the UKB, the UKB-ESC was formed. As a result, exome data from 200,643 UKB enrollees are now available. These data include ~10 million exonic variants-a rich resource of rare coding variation that is particularly valuable for drug discovery. The UKB-ESC precompetitive collaboration has further strengthened academic and industry ties and has provided teams with an opportunity to interact with and learn from the wider research community.

Exome sequencing and characterization of 49,960 individuals in the UK Biobank.

The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

Size-dependence of the flow threshold in dense granular materials.

The flow threshold in dense granular materials is typically modeled by local, stress-based criteria. However, grain-scale cooperativity leads to size effects that cannot be captured with local conditions. In a widely studied example, flows of thin layers of grains down an inclined surface exhibit a size effect whereby thinner layers require more tilt to flow. In this paper, we consider the question of whether the size-dependence of the flow threshold observed in inclined plane flow is configurationally general. Specifically, we consider three different examples of inhomogeneous flow - planar shear flow with gravity, annular shear flow, and vertical chute flow - using two-dimensional discrete-element method calculations and show that the flow threshold is indeed size-dependent in these flow configurations, displaying additional strengthening as the system size is reduced. We then show that the nonlocal granular fluidity model - a nonlocal continuum model for dense granular flow - is capable of quantitatively capturing the observed size-dependent strengthening in all three flow configurations.

Abdominal cocoon with early postoperative small bowel obstruction: A case report and review of literature in China.

RATIONALE: Abdominal cocoon is a condition in which intestinal obstruction results from the encasement of part or whole of the small bowel by a thick fibrous membrane, giving the appearance of a cocoon. The preoperative diagnosis is difficult to be made and the treatment is still controversial. PATIENT CONCERNS: Here we describe the case of a 62-year-old male presented with a 24-h history of continual colicky abdominal pain, which was accompanied with nausea and vomiting. DIAGNOSIS: Accurate diagnosis of abdominal cocoon was made intraoperatively. INTERVENTIONS: Membrane excision and adhesiolysis were performed and the patient experienced early postoperative small bowel obstruction. Nasointestinal obstruction tube was then installed and bowel function was gradually recovered by the 20th postoperative day. OUTCOMES: The patient recovered well and was discharged from the hospital on the 30th postoperative day LESSONS:: Abdominal cocoon can occur at any age. The possibility of abdominal cocoon should also be considered in infertile patients. Imaging studies may be helpful to make the correct diagnosis, and surgery should be performed for patients with recurrent acute or chronic intestinal obstruction.

Target-specific delivery of oxaliplatin to HER2-positive gastric cancer cells in vivo using oxaliplatin-au-fe3o4-herceptin nanoparticles.

Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin-Au-Fe3O4-Herceptin® acts as a dual-functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8-20 nm Au-Fe3O4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ-potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3-H), 2.97-3.02 (3.80H, t, 2-H) and 2.72-2.76 (3.72H, t, 1-H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH-dependent release characteristic. The active targeting feature of oxaliplatin-Au-Fe3O4-Herceptin was verified in a subcutaneous xenograft mouse model containing SGC-7901 cells via detecting aggregated low intensity in T2-weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin-Au-Fe3O4-Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.

[Effects of siRNAs targeting CD97 immune epitopes on biological behavior in breast cancer cell line MDA-MB231].

OBJECTIVE: To investigate the effects of siRNAs targeting CD97 immune epitopes on proliferation, infiltration, apoptosis and cell cycle of breast cancer cells. METHODS: siRNA sequences targeting CD97EGF and CD97Stalk immune epitopes were designed according to Gene Bank NM_001025160.2 with smart siCatchTM siRNA design software. CD97siRNAs were transfected into MDA-MB231 cells in which CD97 was highly expressed. Highest sensitive CD97EGF and CD97Stalk siRNA were screened by Western blotting. Inverted microscope was used to observe the growth of CD97siRNAs-transfected MDA-MB231 cells; the proliferation activity of MDA-MB231 cells was detected by MTT method; the wound healing assay and Transwell migration test were performed to examine the migration and infiltration ability of CD97EGF and CD97Stalk siRNA-transfected MDA-MB231 cells; the effects of CD97EGF siRNA and CD97Stalk siRNA on cell apoptosis and cell cycle of MDA-MB231 cells were detected by TUNEL and flow cytometry. RESULTS: The growth and proliferation activity of CD97siRNAs-transfected MDA-MB231 cells were significantly lower than those in the control groups, and such differences were more significant in CD97Stalk siRNA-transfected group (all P<0.05); scratch test showed that the wound healing rate was lower in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); Transwell migration showed that the number of MDA-MB231 cells crossing through chambers were less in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); no significant difference in cell apoptosis was observed between CD97siRNAs-transfected groups and control groups; cell cycle detection showed that CD97siRNAs-transfected groups had less cells in G0/G1 phase and more cells in S phase compared with the control groups, and such effect on cell cycle was more marked in CD97Stalk siRNA-transfected group (all P<0.05). CONCLUSIONS: CD97 plays an important role in the cell growth, proliferation, migration and invasion of breast cancer MDA-MB231 cells, and compared with CD97EGF, CD97Stalk may have more effective inhibitory effects on cellular malignant behaviors.

Anatomic isolated caudate lobectomy: Is it possible to establish a standard surgical flow?

AIM: To establish the surgical flow for anatomic isolated caudate lobe resection. METHODS: The study was approved by the ethics committee of the Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU). From April 2004 to July 2014, 20 patients were enrolled who underwent anatomic isolated caudate lobectomy at SAHZU. Clinical and postoperative pathological data were analyzed. RESULTS: Of the total 20 cases, 4 received isolated complete caudate lobectomy (20%) and 16 received isolated partial caudate lobectomy (80%). There were 4 cases with the left approach (4/20, 20%), 6 cases with the right approach (6/20, 30%), 7 cases with the bilateral combined approach (7/20, 35%), 3 cases with the anterior approach (3/20, 15%), and the hanging maneuver was also combined in 2 cases. The median tumor size was 5.5 cm (2-12 cm). The median intra-operative blood loss was 600 mL (200-5700 mL). The median intra-operative blood transfusion volume was 250 mL (0-2400 mL). The median operation time was 255 min (110-510 min). The median post-operative hospital stay was 14 d (7-30 d). The 1- and 3-year survival rates for malignant tumor were 88.9% and 49.4%, respectively. CONCLUSION: Caudate lobectomy was a challenging procedure. It was demonstrated that anatomic isolated caudate lobectomy can be done safely and effectively.

Effects of targeted CD97 immune epitopes small interference RNA on cellular biological behaviors in MDA-MB231 malignant breast cancer cell line.

Two CD97 immune epitopes, CD97EGF (epidermal growth factor domain) and CD97Stalk (stalk domain), have different distribution patterns in malignant epidermal tumors. However, little is known about the effect of CD97EGF and CD97Stalk immune epitopes in breast cancer metastasis. To explore the effects on cell proliferation, infiltration, apoptosis, and the cell cycle, we used small interfering RNA (siRNA) against CD97EGF and CD97Stalk immune epitopes to knock down CD97 in MDA-MB231 breast cancer cells. Compared with controls, CD97 knockdown caused decreased cell growth, proliferation, migration, infiltration, and altered distribution of the percentage of cells in G0/G1 and S phase. We suggest that the potential mechanism of CD97EGF and CD97Stalk immune epitopes on the biological behaviors of MDA-MB231 breast cancer cells may be related to the altered number of N-terminal glycosylation sites, which influence the stability and signaling intensity of CD97 heterodimers.

Clinical treatment of gastrinoma: A case report and review of the literature.

Gastrinoma is a gastrin-secreting tumor that is associated with Zollinger-Ellison syndrome. The majority of cases occur in the pancreas, followed by the duodenum. Early diagnosis is difficult due to the relative rarity of the tumor and the lack of specific symptoms. In the current study, a 68-year-old female patient presented at the Second Affiliated Hospital, Zhejiang University (Hangzhou, China) due to intermittent abdominal pain and watery diarrhea. The patient was treated by surgical resection and was pathologically diagnosed with a well-differentiated pancreatic neuroendocrine tumor (gastrinoma; grade 1). No evidence of recurrence was observed during 1 year of follow-up. Furthermore, a review of the Chinese literature was performed, which analyzed an additional 17 published cases of gastrinoma. The tumor size ranged between 0.5×0.5 cm and 7.5×6.3×5.1 cm. The pancreas was the most common site of occurrence, accounting for 72% (13/18) of cases, followed by the duodenum (28%; 5/18). The most common initial symptom was abdominal pain (89%; 16/18), followed by diarrhea (56%; 10/18). In 18 cases, including the present case and 17 previous cases, the level of gastrin ranged between 137 and 1,550 pg/ml (normal range, 5-100 pg/ml). Of the 17 previous cases, 11 patients underwent surgery and 6 patients received conservative therapy due to metastasis or patient choice. Overall, gastrinoma remains a rare disease. Complete removal of the lesion is the standard curative treatment and conservative treatment is only recommended for patients unsuitable for surgery or for those with widespread metastasis.

Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma.

Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (-) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (-) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (-) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (-) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets.

CD97 promotion of gastric carcinoma lymphatic metastasis is exosome dependent.

BACKGROUND: CD97 knockdown impairs the metastatic capacity of SGC-7901 gastric cancer cells. However, the role of CD97 in the distant lymphatic premetastatic niche formation of gastric cancer remains unknown. METHODS: Exosomes and the soluble fraction were isolated from SGC-L (an SGC-7901-cell-derived highly lymphatic metastatic cell line) and CD97-knockdown (SGC-L/CD97-kd) cells, and were co-cultured with gastric cancer cells. The metastatic capacity of the two cell lines was evaluated in vitro and in a footpad lymph node metastasis mouse model. Premetastatic-niche-formation-related proteins were examined immunohistochemically. RESULTS: CD97 expression was ninefold higher in SGC-L cells than in SGC-7901 cells. In vitro, exosomes or conditioned medium from the SGC-L cells enhanced cell proliferation (20 % increase) and invasion (30 % increase) as compared with that from SGC-L/CD97-kd cells (p < 0.01). Intrafootpad injections of SGC-L, but not SGC-L/CD97-kd exosomes or conditioned medium, strongly promoted SGC-L and SGC-L/CD97-kd cell accumulation in the draining lymph nodes (p < 0.01) and increased CD55, CD44v6, α5ß1, CD31, epithelial cell adhesion molecule, and CD151 expression. Although the SGC-L/CD97-kd exosomes alone were insufficient for promotion of metastasis, they were partly aided by the SGC-L-cell-derived soluble fraction. CONCLUSIONS: The CD97 small isoform promotes SGC-L cell lymphatic metastasis exosome dependently, and aided by the soluble fraction, the exosome-dependent CD97 plays a pivotal role in premetastatic niche formation.