This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klagsbrun, M. Articles by Folkman, J. Search for Related Content PubMed PubMed Citation Articles by Klagsbrun, M. Articles by Folkman, J.

Tumor Angiogenesis Activity in Cells Grown in Tissue Culture¹

Department of Surgery, Children's Hospital Medical Center, and The Harvard Medical School, Boston, Massachusetts 02115

Normal, viral transformed, and tumor-derived cells grown in tissue culture and representing different species were tested for their ability to produce an extracellular tumor angiogenesis factor (TAF). TAF was assayed by measuring the host-mediated vascular response of the chorioallantoic membrane to TAF preparations. All of the viral transformed and tumor-derived cells tested, including SVT2, SVW126, Walker 256 rat carcinoma, B-16 mouse melanoma, human glioblastoma, and human meningioma cells, produced TAF.

The potency of the TAF preparations, as measured by the number of cells needed to induce a positive vascular response on the chorioallantoic membrane, varied from cell line to cell line. The most potent cells tested were the glioblastoma and meningioma brain tumor cells. Since these brain tumors are found to be the most highly vascularized tumors in vivo, it was concluded that a correlation exists between the vascularity of a tumor in vivo and the potency of TAF in vitro.

There was no detectable angiogenesis activity induced by density-inhibited BALB/c primary mouse embryo or early-passage human skin fibroblasts, even when relatively large numbers of cells were used to make a sample. However, density-inhibited BALB/c 3T3 and W138 human embryonic lung fibroblasts, two cell lines widely regarded as demonstrating "normal" growth behavior in culture, produced TAF. From these and other observations, it was suggested that BALB/c 3T3 and W138 are not fully "normal" cells. Furthermore, it was suggested that the production of TAF is an early event in the cell transformation process that precedes the loss of density inhibition of growth in vitro.

¹ Supported by National Cancer Institute Grants CA-14019 and CB-43942.

Received 7/24/75. Accepted 9/16/75.

This article has been cited by other articles:

				T. A. Gorr, T. Tomita, P. Wappner, and H. F. Bunn Regulation of Drosophila Hypoxia-inducible Factor (HIF) Activity in SL2 Cells: IDENTIFICATION OF A HYPOXIA-INDUCED VARIANT ISOFORM OF THE HIF{alpha} HOMOLOG GENE similar J. Biol. Chem., August 20, 2004; 279(34): 36048 - 36058. [Abstract] [Full Text] [PDF]

				S. Lavista-Llanos, L. Centanin, M. Irisarri, D. M. Russo, J. M. Gleadle, S. N. Bocca, M. Muzzopappa, P. J. Ratcliffe, and P. Wappner Control of the Hypoxic Response in Drosophila melanogaster by the Basic Helix-Loop-Helix PAS Protein Similar Mol. Cell. Biol., October 1, 2002; 22(19): 6842 - 6853. [Abstract] [Full Text] [PDF]

				R Montesano, M. Pepper, and L Orci Paracrine induction of angiogenesis in vitro by Swiss 3T3 fibroblasts J. Cell Sci., January 8, 1993; 105(4): 1013 - 1024. [Abstract] [PDF]

				S. Salahuddin, S Nakamura, P Biberfeld, M. Kaplan, P. Markham, L Larsson, and R. Gallo Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro Science, October 21, 1988; 242(4877): 430 - 433. [Abstract] [PDF]

				J Folkman and M Klagsbrun Angiogenic factors Science, January 23, 1987; 235(4787): 442 - 447. [Abstract] [PDF]

				S. DeCarvalho Angiokines, Angiogenesis and Angiolymphoproliferative Syndromes (ALPS) Angiology, January 1, 1983; 34(4): 231 - 243. [Abstract] [PDF]

				P. Noguchi, J. Johnson, R O'Donnell, and J. Petricciani Chick embryonic skin as a rapid organ culture assay for cellular neoplasia Science, March 3, 1978; 199(4332): 980 - 983. [Abstract] [PDF]