Tumor formation by a human pre-B leukemia cell line in scid mice is enhanced by matrigel and is associated with induction of CD10 expression.
We have previously demonstrated the engraftment of human pre-B acute lymphoblastic leukemia (ALL) cells injected intravenously into irradiated scid mice. We now report on the ability of the reconstituted extracellular matrix, Matrigel, to promote the formation of subcutaneous tumors in non-irradiated scid mice by a CD10- pre-B ALL cell line termed G2. Lymphatic tumors infiltrating the dermis were seen in all eight mice sacrificed 10-13 weeks after the co-injection of G2 cells and Matrigel but in only 2/8 mice injected with leukemic cells alone. Infiltration of bone marrow, spleen, thymus, lung and liver was observed earlier and was more extensive in the Matrigel-treated group. The tumor cells derived from Matrigel-treated mice could be passaged in vitro and their colony-forming ability was higher than that of the original G2 line. When re-injected intravenously into non-irradiated scid mice, the tumor cells invaded the thymus earlier than did the G2 cells. The expression of CD10/neutral endopeptidase was induced at high levels in all tumors, in Matrigel or non Matrigel-treated animals. This up-regulation was transient as the tumor variants grown in vitro or in vivo lost expression of CD10. However, 6-8 weeks later, induction of CD10 was observed on both tumor variants and parental G2 cells growing in the thymus and at a lower level on cells in bone marrow and spleen. Culturing G2 cells in vitro at high density or in the presence of documented growth-promoting cytokines such as IL-3, IL-6, IL-7, and GM-CSF did not stimulate the expression of CD10 mRNA. The induction of this surface endopeptidase was thus associated with growth of leukemic cells in the specific microenvironments provided by the lymphoid tumors and the thymus in scid mice. The function of CD10 might be related to the hydrolysis of peptides which are critical in regulating interactions between adjacent pre-B cells, the stromal microenvironment and the transduction of growth and/or differentiation signals.
Division of Immunology/Cancer Research, Hospital for Sick Children, Toronto, Canada.
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E
Ishii
A
A
Greaves
T
T
Grunberger
M H
MH
Freedman
M
M
Letarte
D000818:Animals; D003094:Collagen / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D017254:Leukemic Infiltration; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015260:Neprilysin / Q000096:biosynthesis*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology*; D011509:Proteoglycans / Q000494:pharmacology*; D013950:Thymus Gland / Q000473:pathology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D015260:Neprilysin