INVESTIGADORES
BOLONTRADE Marcela Fabiana
congresos y reuniones científicas
Título:
Bone Marrow derived Mesenchymal Stromal Cells recruitment in a T Cell Lymphoblastic Leucemia (T ALL) tumor model
Autor/es:
AMORÓS, MARIANA A.; GUTIÉRREZ, LUCIANA; CAYROL, MARIA FLORENCIA; DIAZ FLAQUE, MARIA CELESTE; SEVLEVER, GUSTAVO; PODHAJCER, OSVALDO.; CERCHIETTI, LEANDRO; CREMASCHI, GRACIELA; BOLONTRADE, MARCELA F.
Lugar:
Estocolmo
Reunión:
Simposio; 13th Annual Meeting- International Society for Stem Cell Research (ISSCR); 2015
Institución organizadora:
International Society for Stem Cell Research (ISSCR)
Resumen:
Mesenchymal Stem Cells (MSCs) are components of the tumor stroma with the ability to actively modulate the tumor microenvironment. This is due to a number of biological properties which include migration, differentiation, immunomodulation and angiogenesis enhancing. In order to study the contribution of human bone marrow derived­ MSCs to tumor stroma formation we established a new in vivo model for T cell lymphoblastic leukemia (T­ALL) in SCID mice using the human cell line CUTLL­1 (Columbia University T­cell Lymphoblastic Lymphoma 1). In contrast to previous models, CUTLL­1 displays biological responses to NOTCH inhibition thus representing the disease?s etiology and serving as a relevant model for pre­clinical and drug screening assays. We studied the incorporation of MSCs into the tumor stroma by measuring the homing capacity of systemically delivered pre­labelled MSCs (DiR+/CMDiI+). Biodistribution was analysedthrough in vivo imaging and fluorescence microscopy. Tumors developed after subcutaneous inoculation of a minimum dose of 2x10e7tumor cells becoming visible 2.5 weeks post­inoculation. We intravenously administered pre­labeled MSCs (1x10e6 cells) into lymphomabearingmice. Infrared signal associated to MSCs homing reached the highest values at smallest tumor volume (4,03x10e5±0,37x10e5p/sec/cme2/sr and 1193±249.1 mme3 tumor volume VS. 0,62x10e5 p/sec/cme2/sr and 2848 mme3 tumor volume) indicating a negativecorrelation between tumor size and MSCs homing ability and pointing at the high homing MSCs capacity into a niche of haematologicalneoplasic cells. Microscopic examination revealed MSCs incorporation as tumor stromal cellular elements, with a perivascular location.Microenvironmental tumor factors may directly affect cell migration and promote tumor progression. We demonstrated that MSCs displayeda high chemotactic response to soluble factors present in the lymphoblastic tumor cells conditioned medium. This coincides with the high MSCs in vivo tumor homing response. Our data suggests that tumor recruited MSCs may be involved in tumor development in this model.By discerning the mechanisms that govern MSCs/tumor cells cross­talk we could contribute to elucidate underlying mechanisms involved in tumor stroma transformation and acquired metastatic properties.