Abstract
The extracellular matrix (ECM) is abnormal in breast tumors and has been reported to contribute to breast tumor progression. One factor, which may drive ongoing matrix synthesis in breast tumors, is the loss of stromal caveolin-1 (cav-1), a scaffolding protein of caveolae, which has been linked to breast tumor aggressiveness. To determine whether loss of cav-1 results in the abnormal expression of matrix proteins, mammary glands from cav- 1-/- and cav- 1 +/+ mice were investigated for differences in expression of several ECM proteins. In addition, the presence of myofibroblasts, changes in the vessel density, and differences in duct number and size were assessed in the mammary glands of both animal models. Using immunohistochemistry, expression of fibronectin, tenascin-C, collagens and αSMA were significantly increased in the mammary glands of cav-1-/- mice. Second harmonic generation revealed more organized collagen fibers in cav-1 -/- glands and supported immunohistochemical analyses of increased collagen abundance in the glands of cav-1 -/- mice. Analysis of the ductal structure demonstrated a significant increase in the number of proliferating ducts in addition to significant increases in the duct circumference and area in cav-1 -/- glands compared to cav- 1 +/+ glands. Differences in microvessel density weren’t apparent between the animal models. In summary, we found that the loss of cav-1 resulted in increased ECM and α-SMA protein expression in murine mammary glands. Furthermore, we found that an abnormal ductal architecture accompanied the loss of cav-1. These data support a role for cav-1 in maintaining mammary gland structure.
Highlights
Caveolin-1 is the main structural protein of caveolae [1], 50-100nm sized invaginations in the plasma membrane [2], responsible for macromolecular transcytosis [3] and regulation of signal transduction [4, 5]
Increased fibronectin expression has been shown to both accompany breast tumorigenesis and support breast tumor progression [32, 37,38,39]
These results demonstrate that the loss of cav-1 promotes the increased expression of peri-ductal and adipose stromal fibronectin in murine mammary glands and further indicates that the overall abundance of fibronectin is greater in cav-1 -/- glands
Summary
Caveolin-1 (cav-1) is the main structural protein of caveolae [1], 50-100nm sized invaginations in the plasma membrane [2], responsible for macromolecular transcytosis [3] and regulation of signal transduction [4, 5]. Cav-1-/- mice crossed with tumor prone MMTV/PyMT mice were reported to have an accelerated appearance of dysplastic foci in mammary glands [13] and were later shown to have an increased number of lung metastases [14]. Together, these studies indicate that the loss of cav-1 is an important driver of breast tumor progression. Recent efforts have been aimed at understanding the contribution of cav-1 toward tumor growth, it remains unknown whether the loss of cav-1 is associated with alterations in the stromal architecture of the gland, a phenomenon that has been extensively reported to accompany breast tumor progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
