TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Zhou, Zhuan; Ran, Yuliang; Hu, Hai; Pan, Jian; Li, Zhifeng; Chen, Li-Zhao; Sun, Lichao; Peng, Liang; Zhao, Xi-Lu; Lan, Yu; Sun, Lixin; Yang, Zhihua

doi:10.1007/s10585-008-9168-0

Cited by 57 publications

(42 citation statements)

References 38 publications

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“…In addition we have shown earlier that the expression of Co-029/tspan8 is associated with a poor prognosis in colorectal cancer (Greco et al, 2010). Similar observations have been made for esophageal (Zhou et al, 2008) and hepatocellular carcinoma (Kanetaka et al, 2001). …”

Section: Introductionsupporting

confidence: 82%

Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model

et al. 2014

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New therapeutic agents are needed in digestive tract tumors. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumors, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don't express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co-029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumor cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic applications.

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Section: Introductionsupporting

confidence: 82%

Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model

et al. 2014

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“…Although the overexpression of tetraspanin 8 has been described in relation to several human cancers [10][11][12][13], and it has been also reported that TSPAN8 mRNA is upregulated in the GC tissues compared to the normal gastric tissues by microarray analysis [14], the significance of tetraspanin 8 protein in GC remains unclear. Immunohistochemical analysis revealed that tetraspanin 8 protein was expressed in GC cells and that 72 (34 %) of 210 GC cases were positive for tetraspanin 8.…”

Section: Discussionmentioning

confidence: 99%

“…TSPAN8 encodes tetraspanin 8 protein, which is a member of the tetraspanin family. It has been reported that TSPAN8 is highly expressed in several types of human cancer [10][11][12][13][14]. Tetraspanins are involved in adhesion, motility, matrix modulation, and cell fusion [9].…”

Section: Generation Of the Mkn-45 Cast Librarymentioning

confidence: 99%

“…TSPAN8 encodes tetraspanin 8 protein, which is a member of the tetraspanins, a family of proteins that crosses the membrane four times and is involved in numerous biological processes [9]. In human cancers, overexpression of tetraspanin 8 has been reported in relation to hepatocellular carcinoma [10], pancreatic cancer [11], colon cancer [12], and esophageal cancer [13]. It has been also reported that TSPAN8 mRNA is upregulated in the GC tissues compared to normal gastric tissues by microarray analysis [14].…”

Section: Introductionmentioning

confidence: 99%

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TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

et al. 2015

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Background Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, will be useful biomarkers for cancer diagnosis and therapeutics. Methods To identify novel genes encoding transmembrane protein specifically expressed in GC, we generated an Escherichia coli ampicillin secretion trap (CAST) library from diffuse-type GC cell line MKN-45. CAST is a survival-based signal sequence trap method that exploits the ability of mammalian signal sequences to confer ampicillin resistance to a mutant b-lactamase lacking the endogenous signal sequence. Results By sequencing 1,536 colonies, we identified 23 genes encoding the transmembrane protein present in GC. Among these genes, TSPAN8 (also known as CO-029 and TM4SF3) gene, which encodes transmembrane protein tetraspanin 8, was emphasized as a candidate. Immunohistochemical analysis of tetraspanin 8 in human GC tissues revealed that 72 (34 %) of 210 GC cases were positive for tetraspanin 8, and microvessel density was significantly higher in tetraspanin 8-positive GC than in tetraspanin 8-negative GC. Furthermore, univariate and multivariate analyses revealed that tetraspanin 8 expression is an independent prognostic classifier of patients with GC. TSPAN8 knockdown by siRNA reduced the invasion of GC cell line. The reduction of invasiveness was retrieved by the tetraspanin 8-containing exosome. Conclusion These results suggest that tetraspanin 8 is involved in tumor progression and is an independent prognostic classifier in patients with GC.

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“…Differences in the tetraspanin microdomain composition account for the abilities of individual tetraspanins to either promote or suppress immune responses (Veenbergen and van Spriel, 2011). TM4SF3, a member of tetraspanin family, was reported to be overexpressed in esophageal carcinomas and was involved in cancer metastasis (Zhou et al, 2008). The relationship between TM4SF3 overexpression and early relapse may be due to the regulation of antitumor immunity.…”

Section: Discussionmentioning

confidence: 99%

EVI2B,ATP2A2,S100B,TM4SF3, andOLFM4As Potential Prognostic Markers for Postoperative Taiwanese Colorectal Cancer Patients

Wang

Tok

Chang

et al. 2012

DNA and Cell Biology

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Undetected micrometastasis may play a key role in the early relapse of colorectal cancer (CRC) patients. The aim of this study was to detect circulating tumor cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic chip array (WEnCA) and analyze 15 candidate genes associated with CRC carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by membrane array and direct sequencing. We constructed a WEnCA platform including five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in 30 clinically confirmed CRC relapse patients. Postoperative relapse was significantly correlated with gene overexpression, including EVI2B (p=0.001, OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3 (p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4), we could detect CTCs presenting these genotypes in relapsed CRC patients. The sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively. The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 could be potential prognostic markers for CRC patients.

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TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Cited by 57 publications

References 38 publications

Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model

Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model

TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

EVI2B,ATP2A2,S100B,TM4SF3, andOLFM4As Potential Prognostic Markers for Postoperative Taiwanese Colorectal Cancer Patients

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