Dottorato in Medicina Molecolare

Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential.

Gurrapu S., Pupo E., Franzolin G., Lanzetti L., Tamagnone L.

Cell Death Differ. 2018 Mar 19. doi: 10.1038/s41418-018-0097-4.

ABCD National PhD Meeting 2018, Salerno 22-24 March 2018

PlexinB1 expression in the tumour microenvironment is critically involved in the metastatic dissemination of breast cancer cells

Giulia Franzolin1,2, M. Accardo1, G. Cagnoni1,2, L.Tamagnone1,2
1Lab. of Cancer Cell Biology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo (TO), Italy
2Dept of Oncology, Univ. of Turin, c/o IRCCS, Candiolo (TO), Italy

Increasing evidence suggests that semaphorin signalling can play an important role in tumour growth and metastatic progression (reviewed by Tamagnone, Cancer Cell, 2012). Previous work demonstrated that syngeneic breast cancer cells engraftment in Semaphorin4D (Sema4D) knock-out mice showed impaired tumour growth and vessels maturation (Sierra et al, J Exp Med, 2008). Indeed, Sema4D is a recognized pro-angiogenic factor (Conrotto et al, Blood, 2005). The main receptor for Sema4D is PlexinB1; however, the role of PlexinB1 in the tumour microenvironment is poorly characterized. Notably, we have previously generated PlexinB1 knock-out mice, which do not display major developmental or angiogenesis defects (Fazzari et al., BMC Dev Biol, 2007). Now we found that the ability of highly metastatic 4T1 breast cancer cells to grow tumour masses when transplanted in syngeneic PlexinB1-deficient mice is partly impaired, although tumour-induced angiogenesis is not reduced. Moreover, PlexinB1 expression in the microenvironment seems to be critical for tumour metastatic dissemination. This is not due to increased cancer cell ability to extravasate and colonize the lungs, thereby suggesting the involvement of a metastasis-promoting mechanism at the level of primary tumours. Our working hypothesis postulates that PlexinB1 may be partly redundant with other Sema4D receptors (such as PlexinB2) for angiogenesis and other mechanisms supporting tumour growth, but it is specifically implicated to regulate metastatic dissemination. Further experiments are ongoing, aimed at investigating stromal cells recruitment in the tumour microenvironment.

Enabling technologies in 3D cancer organoids - Unito Polito Cancer Conference Series

Via Nizza 52, Turin. March 8-9, 2016

CancerTo-Imaging of cancer dynamics - II Unito Polito Cancer Conference Series

via Verdi 9 - Turin. March 7-9, 2018