%0 Journal Article
%T Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer.
%A Park SG
%A Ji MJ
%A Ham IH
%A Shin YH
%A Lee SM
%A Lee CH
%A Kim E
%A Hur H
%A Park HM
%A Kim JY
%J J Cancer Res Clin Oncol
%V 149
%N 8
%D Jul 2023 20
%M 36125535
%F 4.322
%R 10.1007/s00432-022-04361-y
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.