Matrigel modulates a stem cell phenotype and promotes tumor formation in a mantle cell lymphoma cell line

Abstract

Tumors may be maintained by subpopulations of cells possessing stem cell-like properties. We evaluated the stem cell-like and tumor-forming properties of side population (SP) and CD133+/ CD44+ cells in Granta 519, a human mantle cell lymphoma cell line. The in-vitro Cobblestone Area Forming Cell (CAFC) assay, designed to detect stem and progenitor cells, revealed that SP cells contained the greatest proportion of stem cell-like cells. The addition of Matrigel to CAFC assays of SP and non-SP cells both in- creased their respective stem cell frequencies in comparison to those cultures without Matrigel, and additionally resulted in observed stem cell frequencies which were the same between SP and non-SP cells. Contrary, Matrigel decreased the stem cell frequencies of CD133+/CD44+ or CD133?/CD44? cells. In-vivo assays revealed tu- mor formation from Matrigel-mixed SP and non- SP cells, and in one instance, occurred with as few as one Matrigel-mixed SP cell. Vehicle-mixed injections of SP and non-SP tumor cells resulted in tumor formation from SP cells only. Tumor formation did not occur from Matrigel nor hya- luronan (cellular substrate for CD44-expressing cells)-mixed populations of CD133+/CD44+ or CD133?/CD44? cells. These data demonstrate that Matrigel modulates a stem cell phenotype and promotes tumor formation from SP and non- SP cells. The tumor micro-environmental niche and tumor cell to micro-environmental interac- tions may be important future targets for novel chemotherapeutic agents.