Identification of Galectin-1 as a Critical Factor in Function of Mouse Mesenchymal Stromal Cell-Mediated Tumor Promotion

Abstract

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.

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

“…The secreted TSG6 is one of the most important, MSC-derived soluble mediator with anti-inflammatory and immunosuppressive activity in vitro, as well as in vivo [45]. It is also important to note that changes in the cytokine levels we measured reflect alterations in the activation of MΦs only as several laboratories proved that MSCs are not capable of producing IL-10 [46] or TNF even after treatment with TLR agonists [47]. In accordance with these findings, we could not detect TNF and IL-10 production in MSC control wells even when LPS or IFN was present.…”

Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population

“…Mesenchymal stem cells were isolated from bone marrow of one C57BL/6 mouse and characterized as described previously [18,19]. The cells were cultured in DMEM (Gibco ® ) supplemented with 10% fetal bovine serum (FBS) (Gibco In some experiments, MSCs were pre-treated with a mixture of 100 ng/mL mouse recombinant IFN-γ (R&D Systems) and 50 ng/mL TNF-α (kindly provided by Duda E of HAS, BRC Hungary) [22] for 24 h then washed twice with CM and T-cell proliferation was tested as described above.…”

Novel role for galectin-1 in T-cells under physiological and pathological conditions

“…Isolation, characterization and maintenance of murine bone marrow mesenchymal stem cells (BMMSC) were carried out as described previously [25].…”

“…The separated proteins were electro-transferred onto nitrocellulose membrane (Whatman, GE Healthcare). After blocking with 3% gelatin (Sigma) in Tris buffered saline (TBS)/0.05% Tween 20, the membrane was incubated with rabbit anti-mouse Gal-1 antibody [25] or rabbit anti-actin antibody (Abcam, Cambridge, UK) and then with HRP-conjugated swine anti-rabbit IgG (Dako, Glostrup, Denmark). Immunoreactive proteins were visualized using the ECL Plus detection system (Amersham Pharmacia Biotech, GE Healthcare) on X-ray film (Agfa, Morstel, Belgium).…”