{Reference Type}: Journal Article
{Title}: Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer.
{Author}: Park SG;Ji MJ;Ham IH;Shin YH;Lee SM;Lee CH;Kim E;Hur H;Park HM;Kim JY;
{Journal}: J Cancer Res Clin Oncol
{Volume}: 149
{Issue}: 8
{Year}: Jul 2023 20
{Factor}: 4.322
{DOI}: 10.1007/s00432-022-04361-y
{Abstract}: <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.