Impaired capsule formation of tumors in periostin-null mice.
Being a secreted protein, periostin is a multifunctional matricellular glycoprotein. In vitro, periostin has the ability to promote the proliferation and migration of fibroblasts. Previously, it was demonstrated that periostin is mainly produced by cancer-associated fibroblasts or tumor stromal cells. In the present study, we show that periostin regulates capsule formation in a positive manner and inhibits tumor growth. Consistent with a previous finding, several tumor cell lines did not exhibit expression of periostin in vitro or in vivo; and the growth of tumors that had been allografted into periostin -/- mice was significantly accelerated compared with that of the same kind of tumors grafted into periostin +/+ mice. Immunostaining and biochemical analyses revealed that mature collagen was detected abundantly in the capsules and interstitium of the wild-type-grafted tumors but not in those of the periostin -/- grafted tumors. Moreover, the number of activated tumor stromal cells was decreased significantly in the periostin -/- grafted tumors. Our studies suggest that host-derived periostin negatively regulates tumor growth by promoting capsule formation and by mediating changes in the deposition and organization of the tumor microenvironment coordinated by periostin-producing stromal cells.
Shimazaki
Masashi
M
Department of Biological Information, Tokyo Institute of Technology, 4259-B-33 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Kudo
Akira
A
D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology*
D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse