Type III Collagen Directs Stromal Organization and Limits @entity3 in a XXXX Model of @entity0 .

@entity1 @entity0 @entity5 @entity19 @entity189 @entity3
UNASSIGNED: Breast cancer @entity3 is the leading cause of @entity5 in @entity1 worldwide. Collagen in the @entity5 microenvironment plays a crucial role in regulating @entity5 progression. We have shown that type III collagen (Col3), a component of @entity5 stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that @entity5 developed at a higher frequency in Col3(+/-) @entity19 compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on @entity5 behavior, using the @entity19 @entity189 cell line 4T1. Notably, @entity5 volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3(+/-) @entity19 compared to Col3(+/+) littermates. By using @entity19 (4T1) and @entity1 (MDA-MB-231) @entity0 cells grown in Col3-poor and Col3-enriched microenvironments in  vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in  vitro and in @entity5 in  vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the @entity5 microenvironment by suppressing @entity3 -promoting characteristics of the @entity5 -associated stroma.
