Fibroblast growth factor 2 enhances BMSC stemness through ITGA2-dependent PI3K/AKT pathway activation.

Bone marrow-derived mesenchymal stem cells (BMSC) are promising cellular reservoirs for treating degenerative diseases, tissue injuries, and immune system disorders. However, the stemness of BMSCs tends to decrease during in vitro cultivation, thereby restricting their efficacy in clinical applications. Consequently, investigating strategies that bolster the preservation of BMSC stemness and maximize therapeutic potential is necessary. Transcriptomic and single-cell sequencing methodologies were used to perform a comprehensive examination of BMSCs with the objective of substantiating the pivotal involvement of fibroblast growth factor 2 (FGF2) and integrin alpha 2 (ITGA2) in stemness regulation. To investigate the impact of these genes on the BMSC stemness in vitro, experimental approaches involving loss and gain of function were implemented. These approaches encompassed the modulation of FGF2 and ITGA2 expression levels via small interfering RNA and overexpression plasmids. Furthermore, we examined their influence on the proliferation and differentiation capacities of BMSCs, along with the expression of stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, and sex determining region Y-box 2. Transcriptomic analyzes successfully identified FGF2 and ITGA2 as pivotal genes responsible for regulating the stemness of BMSCs. Subsequent single-cell sequencing revealed that elevated FGF2 and ITGA2 expression levels within specific stem cell subpopulations are closely associated with stemness maintenance. Moreover, additional in vitro experiments have convincingly demonstrated that FGF2 effectively enhances the BMSC stemness by upregulating ITGA2 expression, a process mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. This conclusion was supported by the observed upregulation of stemness markers following the induction of FGF2 and ITGA2. Moreover, administration of the BEZ235 pathway inhibitor resulted in the repression of stemness transcription factors, suggesting the substantial involvement of the PI3K/AKT pathway in stemness preservation facilitated by FGF2 and ITGA2. This study elucidates the involvement of FGF2 in augmenting BMSC stemness by modulating ITGA2 and activating the PI3K/AKT pathway. These findings offer valuable contributions to stem cell biology and emphasize the potential of manipulating FGF2 and ITGA2 to optimize BMSCs for therapeutic purposes.

Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer.

BACKGROUND: Integrins are transmembrane proteins that mediate cell adhesion to extracellular matrix. Whereas expression of integrin alpha 2 is associated with motility, invasiveness and cellular differentiation in various tumors, the role of integrin alpha 2 in lung cancer has not been studied in detail. The aim of this study was to determine whether and how aberrant integrin alpha 2 expression in non-small cell lung cancer leads to different outcomes. METHODS: We measured expression of integrin alpha 2 by quantitative polymerase chain reaction in 100 samples collected from non-small cell lung cancer patients who had undergone surgical resection. We assigned patients to high and low expression groups and analyzed survival. Cellular morphology, adhesion, proliferation, migration and invasion were examined in human lung cancer cell lines. RESULTS: Among 100 cases, 41 were female, with a median age of 71 years. High expression of integrin alpha 2 in non-small cell lung cancer was associated with lower recurrence-free survival (P = 0.004). Overexpression of integrin alpha 2 in cell lines had no effect on cell proliferation or invasion but resulted in increased cell size (1416 µm2 versus 470 µm2 in H522 cells, P < 0.001; 1822 µm2 versus 1029 µm2 in H661 cells, P = 0.02), adhesion (P < 0.001 in H522 and H661 cells) and migration (gap area filled was 71% versus 36% in H522 cells, P < 0.001; 57% versus 26% in H661 cells, P = 0.001). These changes were suppressed by E7820, an inhibitor of integrin alpha 2. CONCLUSIONS: Integrin alpha 2 may play a significant role in lung cancer adhesion and migration, and may lead to a higher risk of recurrence.

ITGA2 induces STING expression in pancreatic cancer by inducing DNMT1 degradation.

PURPOSE: Integrin alpha 2 (ITGA2, also known as CD49b or VLA-2) is the alpha subunit of a transmembrane receptor for collagens and related proteins. Previously, we found that ITGA2 may regulate immune cell infiltration in pancreatic cancer by inducing PD-L1 expression. As yet, however, whether ITGA2 regulates immune cell infiltration in pancreatic cancer by other mechanisms remains unclear. METHODS: RNA sequencing was performed to identify differentially expressed genes in ITGA2-silenced pancreatic cancer cells. Protein-protein interactions were detected via co-immunoprecipitation. The infiltration level of immune cells was assessed using an immunofluorescence staining assay. RESULTS: We found that ITGA2 can activate the cytosolic DNA-sensing pathway and promote STING expression in pancreatic cancer cells. In addition, we found that ITGA2 induces DNMT1 degradation by disrupting the interaction between DNMT1 and Kindlin2 in pancreatic cancer cells. As a DNA methyltransferase, we found that DNMT1 overexpression induced by ITGA2 silencing significantly up-regulated the methylation level of the STING gene promoter. Finally, ITGA2 silencing combined with DNMT1 inhibitor treatment induced immune cell infiltration in pancreatic cancer. CONCLUSION: Our data indicate that ITGA2 induces STING expression by interacting with DNMT1 and inducing the degradation of DNMT1. ITGA2 silencing combined with DNMT1 inhibitor treatment may be a novel therapeutic strategy for pancreatic cancer.

Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells.

Methotrexate (MTX) is widely used to treat various diseases. However, it induces adverse reactions like serious lung injury, including pulmonary fibrosis. Increasing evidence suggests that epithelial-mesenchymal transition (EMT) in injured alveolar epithelium contributes to the development of the pathophysiological state of the lung. We demonstrated that MTX induced EMT in cultured alveolar epithelial cell lines. Integrin-mediated signaling is considered a significant factor in recognizing the EMT process. However, the relationship between MTX-induced EMT and integrin family members is poorly understood. In the present study, we aimed to clarify the role of integrin in MTX-induced EMT in A549 and NCI-H1299 (H1299) cells by focusing on the integrin alpha 2 (ITGA2) subunit, selected based on our microarray analysis. MTX treatment for 72 h significantly increased the mRNA and cell surface expression of ITGA2 in both cell lines. However, this upregulation by MTX was suppressed by co-treatment with SB431542 and folic acid, which are inhibitors of MTX-induced EMT in A549 cells. The mRNA expression levels of EMT-related genes were more affected in the MTX-treated A549 cells with high ITGA2 expression than in those with low ITGA2 expression. Finally, E7820, an ITGA2 inhibitor, suppressed MTX-induced EMT-related phenotypic changes, such as morphology and mRNA and protein expression of α-smooth muscle actin, a representative EMT marker. These findings suggest that ITGA2 may play a key role in MTX-induced EMT in alveolar epithelial cells.

Integrin Alpha-2 as a Potential Prognostic and Predictive Biomarker for Patients With Lower-Grade Glioma.

Diffuse gliomas are the most common malignant brain tumors with the highest mortality and recurrence rate in adults. Integrin alpha-2 (ITGA2) is involved in a series of biological processes, including cell adhesion, stemness regulation, angiogenesis, and immune/blood cell functions. The role of ITGA2 in lower-grade gliomas (LGGs) is not well defined. Firstly, we downloaded RNA sequencing and relevant clinical information from The Cancer Genome Atlas cohort, the Chinese Glioma Genome Atlas cohort, and related immune cohorts. Next, prognosis analysis, difference analysis, clinical model construction, enrichment analysis, and immune infiltration analysis are performed for this study. These analyses indicated that ITGA2 may have clinical application value and research value in LGG immunotherapy. We also detected the mRNA and protein expression of ITGA2 in three LGG cell lines and normal glial cells using quantitative real-time polymerase chain reaction assay and western blot assay. Our study not only offers a novel target for LGG immunotherapy but also can better comprehend the mechanism of the development and progression of patients with LGG. This study revealed that ITGA2 may be a potential prognostic and predictive biomarker for LGG, which can bring new insights into targeted immunotherapy.

Overexpression of long non-coding RNA00355 enhances proliferation, chemotaxis, and metastasis in colon cancer via promoting GTF2B-mediated ITGA2.

Long non-coding RNAs (LncRNAs) can regulate physiological and pathological functions, exhibiting a wide range of roles in cell biology. Moreover, many lncRNAs are dysregulated in various cancers, including colon cancer. In this study, we investigated the role of the lncRNA LINC00355 in colon cancer, after first establishing its interaction with GTF2B, and ITGA2 on the LncMap database. The predicted relationships between the lncRNA LINC00355, GTF2B, and ITGA2 were identified using luciferase reporter assay, RIP, and ChIP experiments. Western blot analysis and RT-qPCR were applied to determine expression pattern of lncRNA LINC00355 and ITGA2 in colon cancer cells. Additionally, EdU, TUNEL, Cell-adhesion and Transwell assay was used for the detection of the effects of this axis on proliferation, apoptosis, adhesion, chemotaxis and metastasis. LncRNA LINC00355 targeted IGFBP2 through the recruitment of GTF2B. LncRNA LINC00355 was highly expressed in colon cancer cells, and overexpression of lncRNA LINC00355 increased the expression of IGFBP2 and GTF2B, and thereby promoted the proliferation, chemotaxis, invasion, and migration in colon cancer. In summary, downregulation of lncRNA LINC00355 in colon cancer inhibited tumor growth in colon cancer through effects on the GTF2B/IGFBP2 axis.

KLF4 down-regulation resulting from TLR4 promotion of ERK1/2 phosphorylation underpins inflammatory response in sepsis.

Sepsis is a systemic inflammatory response to invading pathogens, leading to high mortality rates in intensive care units worldwide. Krüppel-like factor 4 (KLF4) is an important anti-inflammatory transcription factor. In this study, we investigate the anti-inflammatory role of KLF4 in caecal ligation and puncture (CLP)-induced septic mice and lipopolysaccharide (LPS)-induced RAW264.7 cells and its potential mechanism. We found that KLF4 was down-regulated in CLP-induced septic mice and in LPS-induced RAW264.7 cells, and that its overexpression led to increased survival rates of septic mice along with inhibited inflammatory response in vivo and in vitro. ITGA2B was up-regulated in the setting of sepsis and was inhibited by KLF4 overexpression. ITGA2B knock-down mimicked the effects of KLF4 overexpression on septic mice and LPS-induced RAW264.7 cells. TLR4 promoted the phosphorylation of ERK1/2 and then up-regulated the ubiquitination and the degradation of KLF4, thereby elevating the expression of ITGA2B. Moreover, TLR4 knock-down or treatment with PD98059 (a MEK inhibitor) inhibited inflammatory response in the setting of sepsis in vivo and in vitro. Furthermore, this effect of PD98059 treatment was lost upon KLF4 knock-down. Collectively, these results explain the down-regulation of KLF4 in sepsis, namely via TLR4 promotion of ERK1/2 phosphorylation, and identify ITGA2B as the downstream gene of KLF4, thus highlighting the anti-inflammatory role of KLF4 in sepsis.

Mutational analysis of 3 Glanzmann's thrombasthenia pedigrees / 中华检验医学杂志

Objective To explore the molecular pathogenesis of 3 Glanzmann's thrombasthenia pedigree by using bioinformatics software and provide evidence for in vitro experiments. Methods The genetic analysis of 3 pedigree diagnosed as Glanzmann's thrombasthenia was carried out. Clustalx-2.1 win software was used to analyze the conservatism of mutant sites in homologous sequences. Bioinformatics software such as PolyPhen-2, PROVEAN, SIFT and Mutationtaster was used to analyze the biological effect of mutation. SPDBV software constructed the molecular structure model of mutant protein and evaluated the influence of mutation on protein structure. Results The "new mutations" found in 3 Glanzmann's thrombasthenia pedigree were ITGA2B:c. 814G>C (p. Val272Leu), ITGA2B:c. 432G>A (p. Trp144Ter) and ACTN1:c. 2458A>G (p. Ile820Val). All three mutations were highly conserved among homologous species. Mutationtaster software showed that 3 new mutations were likely pathogenic. PolyPhen-2 and PROVEAN software showed ITGA2B p.Val272Leu and ACTN1 p.Ile820Val were benign and SIFT software showed that ITGA2B p. Val272Leu were likely pathogenic, while ACTN1 p. Ile820Val is benign. The result of SPDBV software showed that the Val272 of ITGA2B was transformed to Leu, neutralizing all the original hydrogen bond. The Trp144 of ITGA2B is transformed to Ter, resulting in the truncated proteins with only 113 amino acid residues. All these mutations affected the molecular structure of GPⅡb, resulting in a decrease ofGPⅡb/Ⅲa expression. When the Ile820 of ACTN1 is transformed to Val, onlyretained the hydrogen bond of Ile820 and Asp822, neutralized the rest hydrogen bond, whichaffected the molecular structure and protein function of ACTN1. Conclusion The mutations of ITGA2B:c.814G>C (p.VAL272LEU), ITGA2B:c.432G>A (p.Trp144Ter) and ACTN1:c.2458A>G (p.Ile820Val) are pathogenic.

Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer.

BACKGROUND: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin α2ß1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells. RESULTS: In this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 µg/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by up-regulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells. CONCLUSIONS: Here, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.

GPla Polymorphisms Are Associated with Outcomes in Patients at High Cardiovascular Risk.

BACKGROUND: Platelet membrane glycoprotein receptors mediate thrombus formation. GP Ia/IIa is an essential platelet integrin receptor. Single-nucleotide polymorphisms (SNPs) of the GP Ia/IIa gene alter GP Ia/IIa expression; however, their influence on cardiovascular disease remains unclear. This study aimed to investigate the effect of the GP Ia/IIa SNPs rs1126643 and rs1062535 on clinical outcomes in a large collective including high-risk patients with cardiovascular disease. METHODS AND RESULTS: GP Ia SNP analysis was performed in 943 patients with symptomatic coronary artery disease. All patients were tracked for all-cause death, myocardial infarction, and ischemic stroke for 360 days. Homozygous carriers of the minor allele showed significantly worse event-free survival when compared with major allele carriers in the complete collective as well as in the subset of high-risk patients (carrying all of the following three risk factors: diabetes type II, hypertension, and hyperlipidemia). There was no significant difference in the subset of low-risk patients (carrying none of the three risk factors). CONCLUSIONS: GPla SNPs are associated with cardiovascular prognosis especially in high-risk patients. Identification of GPIa SNPs is of importance to tailor therapies in patients at already high cardiovascular risk.

Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages.

OBJECTIVE: The aim of this study was to investigate the association between the genetic heterogeneity of platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa-PlA1/PlA2) and spontaneous abortions. STUDY DESIGN: Two hundred and twenty two women with a history of unexplained spontaneous miscarriages and no successful pregnancy, and 60 fertile women serving as controls were genotyped for the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms by pyrosequencing. RESULTS: In comparison with the common alleles homozygotes, GpIa-807T and GpIIIa-PlA2 carriers had an increased risk of fetal loss (OR = 3.36, 95%CI: 1.85-6.11, p < 0.001, and OR = 2.58, 95%CI: 1.30-5.13, p = 0.006, respectively). For subjects who were combined carriers of the GpIa-807T and GpIIIa-PlA2 alleles, the risk increased further (OR = 9.13, 95%CI: 2.99-27.82, p < 0.001). The above ORs were highest for women who were younger than 30 years of age. CONCLUSIONS: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population.

A correlation research between the Integrin alpha 2 (ITGA2)-807 C/T gene polymorphism and diabetic nephropathy / 实用医学杂志

Objective To explore the relation between the Integrin alpha 2 (ITGA2)-807 C/T gene and diabetic nephropathy (DN) in Han nationality in northern part of Guangxi. Methods 206 patients with type-2 diabetes were selected from the hospital. According to the diagnosis of diabetic nephropathy (DN) standards, 206 patients with type-2 diabetes were divided into diabetes without diabetic nephropathy (T2DM) and DN group, and 90 healthy people were selected as normal control (NC) group. The plasma lipid and lipoprotein levels were measured by routine method.And the genotypes and allele frequencies distribution were assessed by Polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP). Results compared with the control group,plasma total cholesterol(TC),triglyceride(TG) and low density lipoprotein-cholesterol (LDL-C) levels in DN group blood were significantly higher (P 0.05). Conclusions The polymorphism of ITGA2-807C/T gene is associated with the development of DN in Han nationality in northern part of Guangxi. The T allele may be a genetic susceptibility genes for DN, which may promote the level of TC high expression and increase the risk of DN.

In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative Stress and α2 and ß1 Integrin Subunits Expression.

BACKGROUND: Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2ß1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction. OBJECTIVES: In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model. MATERIALS AND METHODS: HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 µg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) α2ß1 integrin expression were assayed. RESULTS: CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 µg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of ß1integrin expression was observed in 1 and 10 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells. CONCLUSIONS: The observed reduction of α2ß1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.

Induction of Selective Cell Death of Oral Squamous Carcinoma Cells by Integrin alpha2 Antibody and EGFR Antibody

The significance and expression of Integrin α2β1 in serum of osteosarcoma patients / 中华骨科杂志

Objective To evaluate the expression of Integrin α2β1 in serum of osteosarcoma patients and to investigate the effect of Integrin α2β1 on metastasis of osteosarcoma. Methods Sandwich enzymelinked immunosorbent assay was applied to test Integrin α2β1 in serum of 26 healthy controls (male 16, female 10; age 18-32, average age 23.54±3.82) and 43 osteosarcoma patients (male 28, female 15;age 8-47,average age 18.42±9.10)before and after the surgery and the chemotherapy. The patients included osteoprogenitor cells type in 24 cases, fibroblast type in 9 cases, chondroblast type in 7 cases, and other types in 3cases; with Enneking stage ⅡA in 13 cases, stage ⅡB in 26 cases, stage Ⅲ in 4 cases. Among them, 22 patients receive the neo-adjuvant chemotherapy. After that, we compared the data of different groups. At the same time, in accordance with tumor size, position, clinical stage, histology grade and metastasis situation to categorize groups compared among the groups of serum Integrin α2β1 differences in order to explore its relationship with patients' prognosis and metastasis. Results The Integrin α2β1 of osteosarcoma patients in blood before the surgery was expressed highly. It was significantly higher than the control group. The expression before surgery had significant correlation with osteosarcoma Enneking clinical stages, tumor size and metastasis. And it was independent of tumor position and Dahlin histology grade. The expression of Integrin α2β1 in blood of the osteosarcoma patients after limb salvage surgery decreased significantly. And the expression of Integrin α2β1 in blood of patients receiving new adjuvant chemotherapy was significant differences before and after the chemotherapy. Conclusion The expression of Integrin α2β1 has positive correlation with the occurrence, development and metastasis of the osteosarcoma. It is probably a new biological indicator for diagnosis and estimating prognosis of osteosarcoma. Simultaneously surgery and new adjuvant chemotherapy are still effective methods to treat osteosarcoma.