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Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer

Park, SG | Ji, MJ | Ham, IH  | Shin, YH | Lee, SM | Lee, CH | Kim, E | Hur, H  | Park, HM | Kim, JY
Journal of cancer research and clinical oncology, 149(8). : 4477-4487, 2023
Journal Title
Journal of cancer research and clinical oncology
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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Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Ajou Authors
함, 인혜  |  허, 훈
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