Secretome Analysis Reveals Reduced Expression of COL4A2 in Hypoxic Cancer-associated Fibroblasts with a Tumor-promoting Function in Gastric Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2022 Sep 20

PMID 36125535

Authors

Seo-Gyu Park

Mi-Jung Ji

In-Hye Ham

Yoon-Hee Shin

Su-Min Lee

Chang Hoon Lee

Eunjung Kim

Hoon Hur

Hyun-Mee Park

Jae-Young Kim

Affiliations

Soon will be listed here.

Abstract

Background: Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.

Methods: To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC-MS/MS.

Results: We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.

Conclusions: The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.

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