Cell adhesiveness is related to tumorigenicity in malignant lymphoid cells.

Abstract

Mouse lymphoma cells ($49) that grow in suspension culture were selected for increased tumorigenicity through continuous passages in syngeneic BALB/c mice. Developing tumors were classified as high grade malignant lymphoma, small noncleaved type. Variants were selected from these tumorigenic cells that were able to grow as a monolayer attached to their substrate, resembling, in this respect, fibroblastoid cells. Whereas the tumorigenic suspension-growing parental cells were able to induce progressive tumors with an inoculum as low as 100 cells per mouse, the adherent cells were unable to develop as tumors even at an inoculum of 1 x 108 cells per mouse. In addition, mice inoculated once with live adherent cells were immunized against 1 x 107 suspension-growing cells. Involvement of an immune response in the rejection of tumorigenic $49 cells was suggested by (a) adoptive transfer experiments in which spleen cells from immunized mice protected naive mice and (b) the appearance of antibodies in the sera of immunized syngeneic mice that specifically recognized both adherent and suspension-growing $49 cells and detected differences in [35S]methioninelabeled antigens from these cells. Antibodies raised in rabbits against adherent cells recognized three proteins of 34,000, 61,000, and 72,000 apparent molecular weight in radiolabeled adherent cell extracts that are either absent or present in small amounts in extracts of suspension-growing tumorigenic $49 cells. These findings, taken together with our previous report (Hochman, J., A. Katz, E. Levy, and S. Eshel, 1981, Nature (Lond.), 290:248-249), suggest the $49 system as a novel system for studying growth control in malignant lymphoid cells.The relationship among cell adhesiveness (the ability to adhere to other cells and to extracellular substrata), transformation, tumor development, and the metastatic behavior of malignant cells is a well-known but complex phenomenon that has been studied extensively (l, 3, 5, 9, 18, 20, 24) since Ludford (17) and Cowdry (6) first suggested that membranes of tumor cells had lower general adhesive properties than the normal cells from which they were derived. These previous studies have all been carried out on cells grown as monolayers (i.e., fibroblastoid) attached to their substratum and to each other.We have undertaken to study this relationship in malignant lymphoid cells that grow attached neither to each other nor to their substratum. Our working hypothesis is that if in fibroblasts decreased cell adhesiveness correlates with in-1282 creased tumorigenicity (3, 18) and vice versa, then isolation of adherent variants from malignant lymphoid cells may result in decreased tumorigenicity. Such a model would be of potential significance in the study of in vitro growth regulation of malignant lymphoid cells.To test this approach, we have used $49 cells--a mouse lymphoma cell line of BALB/c origin (13). We have first demonstrated that stable variants can be isolated, characterized by their ability to adhere to their substratu...

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

“…T-25 cells 34,35 were cultured in Dulbecco's modified Eagle medium medium supplemented with 10% heat-inactivated horse serum.…”

An experimental model for infiltration of malignant lymphoma to the eye and brain

“…We have previously used these cells to select for highly tumorigenic suspension-borne variants named T-25 [18,19]. T-25 cells developed progressive tumors (defined as a high-grade malignant lymphoma, small non-cleaved cell type, with a starry-sky appearance) with a median survival of about 14 days, following intraperitoneal (IP) inoculation of 10 7 cells into syngeneic mice.…”

“…T-25 cells developed progressive tumors (defined as a high-grade malignant lymphoma, small non-cleaved cell type, with a starry-sky appearance) with a median survival of about 14 days, following intraperitoneal (IP) inoculation of 10 7 cells into syngeneic mice. From T-25 cells we selected spontaneously developing substrate-adhesive variants, named T-25-Adh, which revealed impaired tumorigenicity (no tumors with up to 10 8 cells per mouse) and enhanced immunogenicity (protection against a challenge with tumorigenic T-25 cells) in immunocompetent mice [18,19]. These cells were subsequently used to study different parameters of growth regulation and immunogenicity [6,20,21,32].…”

Pentoxifylline enhances lung colonization and alters cell adhesion and glycosaminoglycan synthesis by metastatic B16 melanoma cells

“…In addition, compositional or structural changes in the GAG sidechains of proteoglycans from tumour cells have been observed with increasing metastatic potential (Steck et al, 1987;Timar et al, 1987), while correlations between adhesive properties and metastatic potential have been suggested in a number of cell types (Raz et al, 1986;Hochman et al, 1984;Netland and Zetter, 1985).…”