Vascular Cx43 may therefore represent a novel target for anti-angiogenic or vascular normalization strategies. Supported in part by NIH CA138727. Poster No. 159 Investigating
a Role for CCN3 in the Promotion of BIRB 796 nmr CUDC-907 breast Cancer Metastasis to Bone Veronique Ouellet 1,2 , Jenna Fong3, Svetlana Komorova2,3,4, Bernard Perbal5, Danh Tran-Tanh6, Eitan Amir7, Mark Clemons7, Peter Siegel1,2,8 1 Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada, 2 Department of Medecine, McGill University, Montreal, Quebec, Canada, 3 Department of Dentistry, McGill University, Montreal, Quebec, Canada, 4 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada, 5 Research and Development, L’Oreal, Clark, New Jersey, USA, 6 Department of Pathology, The Princess Margaret Hospital, Toronto, Ontario, Canada, 7 Department of Orthopaedic Surgery, The Princess Margaret Hospital, Toronto, Ontario, Canada, 8 Department of Biochemistry, McGill University, Montreal, Quebec, Canada Breast cancer is the most frequent and the second most lethal cancer affecting women in Canada. The skeleton is a common site for breast selleck screening library cancer metastasis; however, the reasons for this
are not fully understood. We have used mouse models to isolate 4 T1 breast cancer cell populations that aggressively metastasize to bone and have compared them to cells that are weakly bone metastatic. Through gene expression profiling, we have identified ccn3 (nov), which is expressed at higher levels in the aggressively bone metastatic cells versus those that weakly metastasize to bone. We have verified that our bone metastatic breast cancer cells overexpress ccn3 mRNA and
that elevated levels of CCN3 protein are detected in the conditioned media of the bone metastatic 4 T1 sub-populations. To determine the relevance of CCN3 expression in human breast cancer, we have interrogated ccn3 expression in publically available gene expression datasets and have observed a correlation between ccn3 expression and the luminal sub-type. These results are interesting in light Pregnenolone of the fact that breast cancers that metastasize to the bone are most likely to be of the luminal subtype. Finally, we have performed immunohistochemical staining of CCN3 in bone metastases derived from patients with breast cancer and have found that CCN3 is expressed in every lesion (20/20). Together, these data implicate CCN3 as an interesting target associated with breast cancer bone metastasis. Given the osteolytic nature of the bone metastases that develop in our 4 T1 breast cancer model, we wished to test the hypothesis that CCN3 plays a causal role in promoting the formation of osteolytic lesions through the inhibition of osteoblast differentiation. Using primary cultures of mouse bone marrow cells, we confirmed that a recombinant CCN3 protein impaired osteoblast differentiation.