R-spondin 3, which activates the WNT pathway, is expressed and secreted by basal mammary cells

TOCCI J; QUAGLINO A.; GODDIO MV; BERARDI D; TODARO L; SREBROW A.; KORDON E

Bariloche

Congreso; Second South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM 2012).; 2012

IFIBYNE-CONICET

R-spondins (RSPOs) are a family of four cysteine-rich secreted proteins with a single thrombospondin type I repeat (TSR) domain. Reportedly, they modulate both the canonical and non-canonical WNT signalling pathways in different cell types. Over the last several years, RSPOs have been implicated in significant processes like embryonic development, tissue differentiation and human diseases, and they have been postulated as potent stem cells growth factors. In addition, we and other groups have determined that RSPOs, particularly Rspo3, are frequently mutated in mouse mammary tumor virus (MMTV)-induced tumors and their over-expression induces cancer initiation and progression. However, little is known about the expression pattern and activity of Rspo3 in the normal mammary gland and in tumors that have not been induced by MMTV. Our results show that Rspo3 is expressed in mouse tumorigenic (not infected with MMTV) and non-tumorigenic mammary cells. Interestingly, we have determined that expression of this protein is lower in luminal than in basal-like mammary cells, in which Rspo3 correlates with vimentin content. Our preliminary data suggest that this protein induces activation of the wnt canonical pathway, although its extracellular presence does not seem to interfere with luminal cell differentiation. Presently, experiments are underway to determine Rspo3 biological role in the commitment, development and differentiation of mammary cell sub-populations.