Integrin ß6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy.

It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvß6 can contribute to malignant behavior of colon cancer. We have found that integrin αvß6 and eIF4E were co-expressed and positively correlated in colon cancer tissues. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major participant in cancer development and progression. However, the regulation of integrin ß6 expression at translational level has never been investigated before. In present study, gene-silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the subsequent experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin ß6 in colon cancer SW480 and HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed. siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of ß6 was markedly suppressed, while mRNA expression of ß6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of ß6, without effect on ß6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and ß6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin ß6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis, and chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin αvß6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.

mRNA expression of somatostatin receptor subtypes SSTR-2, SSTR-3, and SSTR-5 and its significance in pancreatic cancer.

BACKGROUND: The aim of this study is to investigate the expressions of somatostatin receptor (SSTR), SSTR-2, SSTR-3, and SSTR-5, in pancreatic tissue and non-cancerous tissue and elucidate their clinical significance. METHODS: The expression of somatostatin receptor subtypes SSTR-2, SSTR-3, and SSTR-5 messenger RNA (mRNA) in 108 cases of cancer tissue and adjacent tissue in patients with pancreatic cancer was detected by reverse transcriptase polymerase chain reaction (RT-PCR). Expression of SSTR-2, SSTR-3, and SSTR-5 mRNA was evaluated after specimens were taken from selected patients who underwent surgical resection by Whipple's operation. We speculated the clinical significance of the expression of somatostatin receptor (SSTR) subtype genes SSTR-2, SSTR-3, and SSTR-5 in pancreatic tissue and non-cancerous tissue and further elucidated their clinical significance. RESULTS: The expression rates of SSTR-2 mRNA in cancer and adjacent tissue of 108 patients with pancreatic cancer were 81.5% (88/108) and 97.2% (105/108), respectively; SSTR-3 mRNA expression rates were 69.4% (75/108) and 55.6% (60/108). SSTR-5 mRNA expression rates were 13.0% (14/108) and 18.5% (20/108). CONCLUSION: We propose that SSTR-2 plays an important role in clinical implications for patients with pancreatic cancer undergoing somatostatin or its analog therapy.

The clinical significance and underlying correlation of pStat-3 and integrin αvß6 expression in gallbladder cancer.

BACKGROUND: Both phosphorylated signal transducer and activator of transcription 3(pStat-3) and integrin αvß6 can play vital role in the development and progression of cancer. However, little is known about their expression correlation and clinical significance in gallbladder cancer(GBC). OBJECTIVE: The aim of our present study was to investigate the expression of pStat-3 and integrin αvß6, two proteins' correlation and their clinical significance in GBC tissues. RESULTS: The expression of pStat-3 and integrin αvß6 were both significantly associated with T stage, lymph node metastasis status, TNM stage (P=0.008, P=0.000, P=0.000 and P=0.036, P=0.001,P=0.000,respectively). IHC and Western blot showed their expressions in GBC tissues were higher than that in paraneoplastic tissues. Moderate positive correlation existed between the two proteins (r =0.349, P <0.001). The survival analysis by Kaplan-Meier and Cox regression model showed that GBC patients with pStat-3 or integrin αvß6 positive expression had a significantly poorer 2-year survival rate (P = 0.002 and 0.000, the log-rank test, respectively), and either marker could act as unfavorable independent prognostic factors(RR=1.907, P=0.021 and RR=2.046, P=0.038). MATERIALS AND METHODS: The expression levels of pStat-3 and integrin αvß6 were analyzed in GBC cancerous and paraneoplastic tissues of 97 cases via immunohistochemistry(IHC) and further validated by western blot method. Besides, SPSS software was used to observe their clinical significance as well as the two proteins' correlation. CONCLUSION: pStat-3 and integrin αvß6 were indicators of tumor's progression and poor prognosis of patients with GBC. And the further study involving them may provide a helpful therapeutic target in prevention and treatment of GBC patients.

Tumor specific delivery and therapy mediate by integrin ß6-target immunoliposomes for ß6-siRNA in colon carcinoma.

Adjuvant chemotherapy does not achieve the desired therapeutic efficacy in colon cancer as a result of the deficient reaction. Gene therapy using small interfering RNAs (siRNAs) delivered by target delivering system represents a potent and specific strategy in tumor therapy. Integrinß6 is exclusively expressed in malignant colonic epithelia, associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, designing an efficient and targeted delivery system for ß6-siRNA could be a potential approach to improve therapeutic efficacy of colon cancer. Here, we designed the Integrinß6 target immunoliposomes for highly efficient and selective delivery of ß6-siRNA in colon cancer, which consequently resulted in greatly growth suppression, invasion and metastasis of colon cancer cells. Moreover, it was able to greatly inhibit the tumor growing in vivo.