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Gene expression analysis of TGF-beta signaling-disrupting gastric cancer cell line 2MLN

ABSTRACT: Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However, detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE12336 | GEO | 2011/12/30

SECONDARY ACCESSION(S): PRJNA113229

REPOSITORIES: GEO

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Project description:Gastric cancer ranks among the top ten most prevalent tumors worldwide, characterized by substantial heterogeneity and diverse morphological manifestations. Although postoperative histopathological examination serves as the cornerstone for determining Lauren classification, there exists a notable time lag in acquiring Lauren grade through this method. Furthermore, the invasiveness of detection techniques and limited tissue specimens markedly compromise the diagnostic precision of Lauren classification. Moreover, distinct molecular expression profiles exist between intestinal and diffuse types, yet the lack of molecular markers hampers the identification of these subtypes and their underlying mechanisms. Hence, our objective is to unearth biomarkers capable of distinguishing between intestinal and diffuse types and elucidate their mechanistic underpinnings, thereby refining the accuracy and applicability of Lauren classification. This pursuit holds promise for informing prognosis and optimizing treatment strategies for gastric cancer patients. Glycosylation emerges as a pivotal player in gastric cancer pathogenesis. Leveraging bioinformatics analyses on publicly available gastric cancer databases, we identified, at the transcriptomic level, elevated expression of the glycosylation-associated gene GXYLT2 in the diffuse subtype compared to the intestinal subtype. Subsequently, we corroborated these findings at both cellular and clinical tissue levels. Notably, GXYLT2 knockdown attenuated the proliferative, invasive, and sphere-forming capacities of gastric cancer cells in vitro. RNA-seq analysis and cellular validation unveiled that GXYLT2 depletion operates through inhibition of the Wnt/β-catenin signaling pathway. Encouragingly, in vivo validation demonstrated that GXYLT2 knockdown impedes gastric cancer growth. In conclusion, our study positions GXYLT2 as a potential biomarker capable of discerning between intestinal and diffuse subtypes, with prognostic implications in gastric cancer. Furthermore, we elucidate its role in gastric cancer progression via modulation of the Wnt/β-catenin signaling pathway.

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Gene expression analysis of TGF-beta signaling-disrupting gastric cancer cell line 2MLN

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