Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis.
It has been well documented that microenvironment consisting of stroma affects breast cancer progression. However, the mechanisms by which cancer cells and fibroblasts, the major cell type in stroma, interact with each other during tumor development remains to be elucidated. Here, we show that the human cancer-associated fibroblasts (CAFs) had higher activity in enhancing breast tumorigenecity compared to the normal tissue-associated fibroblasts (NAFs) isolated from the same patients. The expression level of hepatocyte growth factor (HGF) in these fibroblasts was positively correlated with their ability to enhance breast tumorigenesis in mice. Deprivation of HGF using a neutralizing antibody reduced CAF-mediated colony formation of human breast cancer cells, indicating that CAFs enhanced cancer cell colony formation mainly through HGF secretion. Co-culture with human breast cancer MDA-MB-468 cells in a transwell system enhanced NAFs to secret HGF as well as promote tumorigenecity. The newly gained ability of these "educated" NAFs became irreversible after continuing this process till fourth passage. These results suggested that breast cancer cells could alter the nature of its surrounding fibroblasts to secrete HGF to support its own progression through paracrine signaling.
Genomics Research Center, Academia Sinica, Taipei, Taiwan Authority.
Shiaw-Wei
SW
Tyan
Wen-Hung
WH
Kuo
Chun-Kai
CK
Huang
Chi-Chun
CC
Pan
Jin-Yuh
JY
Shew
King-Jen
KJ
Chang
Eva Y-H P
EY
Lee
Wen-Hwa
WH
Lee
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D019899:Paracrine Communication; D059016:Tumor Microenvironment / Q000502:physiology*
D017228:Hepatocyte Growth Factor
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