Bone marrow derived mesenchymal stromal cells (MSCs) have recently been implicated
as one source of the tumor-associated stroma, which plays essential role in regulating
tumor progression. In spite of the intensive research, the individual factors in MSCs
controlling tumor progression have not been adequately defined. In the present study
we have examined the role of galectin-1 (Gal-1), a protein highly expressed in tumors
with poor prognosis, in MSCs in the course of tumor development. Co-transplantation
of wild type MSCs with 4T1 mouse breast carcinoma cells enhances the incidence of
palpable tumors, growth, vascularization and metastasis. It also reduces survival
compared to animals treated with tumor cells alone or in combination with Gal-1 knockout
MSCs. In vitro studies show that the absence of Gal-1 in MSCs does not affect the
number of migrating MSCs toward the tumor cells, which is supported by the in vivo
migration of intravenously injected MSCs into the tumor. Moreover, differentiation
of endothelial cells into blood vessel-like structures strongly depends on the expression
of Gal-1 in MSCs. Vital role of Gal-1 in MSCs has been further verified in Gal-1 knockout
mice. By administering B16F10 melanoma cells into Gal-1 deficient animals, tumor growth
is highly reduced compared to wild type animals. Nevertheless, co-injection of wild
type but not Gal-1 deficient MSCs results in dramatic tumor growth and development.
These results confirm that galectin-1 is one of the critical factors in MSCs regulating
tumor progression.
