TITLE:
Matrigel modulates a stem cell phenotype and promotes tumor formation in a mantle cell lymphoma cell line
AUTHORS:
Abigail Hielscher, Timothy McGuire, Dennis Weisenburger, John Graham Sharp
KEYWORDS:
Mantle Cell Lymphoma; Side Population; Tumor-Initiating Cells; Microenvironment
JOURNAL NAME:
Stem Cell Discovery,
Vol.3 No.3,
July
17,
2013
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 increased 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 tumor
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 hyaluronan (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 interactions
may be important future targets for novel chemotherapeutic agents.