Cancer-associated fibroblast-dependent and -independent invasion of gastric cancer cells

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 8; pp. 5309 - 5319
• Main Authors: Kondo, Ryotaro, Sakamoto, Naoya, Harada, Kenji, Hashimoto, Hiroko, Morisue, Ryo, Yanagihara, Kazuyoshi, Kinoshita, Takahiro, Kojima, Motohiro, Ishii, Genichiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2023; Springer Nature B.V
• Subjects: Cancer Research; Collagen; Fibroblasts; Gastric cancer; Hematology; Internal Medicine; Invasiveness; Medicine; Medicine & Public Health; Oncology; Tumor cell lines; Cancer-associated fibroblasts (CAFs); CAFs-independent; Collagen; CAFs-dependent; Invasion
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-022-04484-2

Purpose
Cancer cells are known to exhibit a cancer-associated fibroblast (CAF)-dependent invasive mode in the presence of CAFs. The purpose of this study was to investigate whether intrinsic factors of
gastric
cancer cells influence the CAF-dependent invasive mode of cancer cells.
Methods
We observed dynamic movement of CAFs, and cancer cells, by time-lapse imaging of 2-D and 3-D collagen invasion models, and evaluated invasion modes of gastric cancer cell lines (MKN-7, MKN-45, and HSC44PE). We further examined whether modification of invasive capacity of CAFs can alter invasive mode of MKN-7, and HSC44PE cells.
Results
When MKN-7 and MKN-45 cells were co-cultured with CAFs, CAFs first invade collagen matrix followed by cancer cells (CAF-dependent invasion), whereas HSC44PE cells invaded collagen matrix independent of CAFs’ invasion. Overexpression or suppression of podoplanin in CAFs, respectively, increased or decreased the invasive capacity of CAFs, and significantly increased or decreased the number of invading MKN-7 cells, respectively. CAFs overexpressing a podoplanin mutant, lacking the cytoplasmic domain, had significantly reduced invasive capacity, compared to CAFs overexpressing wild-type podoplanin, and it also reduced the number of invading MKN-7 cells significantly. When HSC44PE cells, and CAFs were co-cultured, changes in the podoplanin expression in CAFs similarly altered the invasive capacity of CAFs, but it did not affect the number of invading HSC44PE cells.
Conclusions
These results indicate that in presence of CAFs, gastric cancer cells exhibit both CAF-dependent and -independent modes of invasion, the determinants of which may depend on the intrinsic properties of the
gastric
cancer cells.