Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis

Abstract

Summary Metastatic variant sublines of the murine large-cell lymphoma cell line RAW 117 were tested for their growth and migration properties in vitro in medium conditioned by soluble factors released from syngeneic mouse liver-, lung-, and brain-derived microvessel endothelial cells. Medium conditioned with hepatic sinusoidal endothelial cells stimulated the growth of highly liver-colonising (RAWl 17-H10) and highly liver-and lung-colonising (RAW117-L17) sublines at higher rates than the poorly metastatic parental line (RAW117-P) (H10>L17>P). Medium conditioned with lung microvessel endothelial cells selectively stimulated the growth of the lung-colonising RAW117-L17 subline. Medium conditioned with brain microvessel endothelial cells showed no growth selectivity, and equivalently stimulated the growth of various RAW117 cell sublines. Medium conditioned with hepatic sinusoidal endothelial cells preferentially promoted the migration of the liver-colonising H10 and L17 sublines, and medium conditioned with lung endothelial cells differentially stimulated the migration of the lung-colonising L17 subline; whereas medium conditioned with brain endothelial cells only slightly stimulated the migration of L17, but not H10 or P cells. Fractionation of medium conditioned with hepatic sinusoidal endothelial cells by DEAE Sephacel anion exchange chromatography revealed that the growth-stimulating activities were clearly separable from migrationstimulating activities. The growth-and migration-stimulating activities released from organ microvessel endothelial cells may be important in determining the ability of RAW 117 cells to selectively form metastatic colonies in particular organs.

Overexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growthin vivo

“…Finally, paracrine stimulation of tumor cells by growth factors from endothelial and stromal cells may have stimulated growth. 38 IGFBP-6 expression correlates with quiescence of myoblasts 13 and IGFBP-6 expression is low or absent in RMS. 6 Further, IGFBP-6 expression is strongly down-regulated in spontaneously metastatic RMS cells compared with non-metastatic parental RMS cells (see additional World Wide Web data in Scholl et al 15 ).…”

Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells

“…It is fundamental to physiologic processes, including embryogenesis, wound repair, and menstruation; it also plays an important role in tumor growth, invasion, and metastasis (4). New vessels promote tumor cell growth by carrying oxygen and nutrients and removing catabolites, whereas endothelial cells secrete growth factors for tumor cells (5) and a variety of matrix-degrading proteinases that facilitate invasion (6). An expanding endothelial surface also gives tumor cells more opportunities to enter the circulation and metastasize (7), whereas the release of antiangiogenic factors by tumor cells may account, at least in part, for control exerted by primary tumors over metastasis (8,9).…”

Do mast cells help to induce angiogenesis in B-cell non-Hodgkin's lymphomas?

“…On the other hand, angiogenesis is fundamental for tumour progression in the form of growth, invasion and metastasis (Folkman, 1995). Microvessels promote growth because they convey nutrients and oxygen and remove catabolites, whereas endothelial cells secrete paracrine growth factors for tumour cells (Hamada et al, 1992). They facilitate invasion because endothelial cells at their tips secrete several extracellular matrix-degrading enzymes, which allow the tumour to spread into and through the adjacent matrix (Mignatti and Rifkin, 1993).…”