Abstract
Consistent with their essential role in cell adhesion to the extracellular matrix, integrins and their associated signaling pathways have been shown to be involved in cell proliferation, migration, invasion and survival, processes required in both tumorigenesis and metastasis. β1-integrins represent the predominantly expressed integrins in mammary epithelial cells and have been proven crucial for mammary gland development and differentiation. Here we provide an overview of the studies that have used transgenic mouse models of mammary tumorigenesis to establish β1-integrin as a critical mediator of breast cancer progression and thereby as a potential therapeutic target for the development of new anticancer strategies.
Highlights
Breast cancer continues to be the most common cancer diagnosed and the leading cause of cancer-related death in women worldwide
Using targeted excision of β1-integrin in luminal epithelial cells where the polyoma virus middle T antigen (PyVmT) oncogene was expressed [55], we have shown that β1-integrin was absolutely required for the induction of mammary tumors
At first, using an approach identical to the aforementioned, mammary epithelial disruption of focal adhesion kinase (FAK) was demonstrated to result in a dramatic reduction in the proliferative potential of PyVmT-transformed cells without exhibiting evidence of enhanced apoptosis. These results demonstrate that FAK is dispensable for the initiation of mammary tumorigenesis, it is still required for the transition of premalignant hyperplasias to carcinomas and their subsequent metastases [54]
Summary
Breast cancer continues to be the most common cancer diagnosed and the leading cause of cancer-related death in women worldwide. Strategies developed against the α5β1 heterodimer, an integrin expressed on the basal surface of myoepithelial mammary ductal cells, led to the development of a rat-anti-mouse blocking antibody able to inhibit the growth of established tumors in multiple xenograft models [95] Volociximab, another blocking antibody against α5β1-integrin that is currently in multiple phase II clinical trials, including as monotherapy in patients with platinum-resistant advanced epithelial ovarian cancer or primary peritoneal cancer [96], was found to significantly inhibit tumor growth when administered intravenously in the rabbit VX2 carcinoma model [97]. These data provide great expectations of enhanced radiation therapy in breast cancer
Sign-in/Register to view highlights & summary 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.
