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Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review

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Summary

Angiogenesis, the process of developing a hemovascular network, is an essential feature of the growth of solid tumors, and is induced by factors secreted by tumor cells. Assay procedures suitable for the investigation of angiogenesis, and for the screening of angiogenesis factors during purification are reviewed; and a number of reports describing the purification of angiogenesis factors, primarily from the rat Walker 256 carcinoma as starting material, are discussed. Work from the authors' laboratory is also presented. Walker 256 cells grown in large-scale culture were the source of a reproducible and homogeneous source of angiogenic material. Factors secreted by these cells were isolated by a series of chromatographic steps. Ion exchange chromatography on carboxymethyl-Sephadex produced two active fractions, one of which was fractionated into several macromolecular species by lectin affinity and hydrophobic adsorption chromatography. The other gave a high mol.wt, active fraction that was resolved into a low mol.wt, active component and a non-angiogenic but possibly carrier molecule with a mol.wt of 140,000. While none of the angiogenic factors were identified chemically, the results demonstrate the existence of both high and low mol.wt tumor-secreted angiogenic substances, confirming the hypothesis for tumor-induced angiogenesis and predicting potential means to interfere with the process of tumor growth.

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Abbreviations

DMEM:

Dulbecco's modified Eagle's medium

FBS:

fetal bovine serum

PBS:

Dulbecco's calcium- and magnesium free phosphate-buffered saline

SDS-PAGE:

sodium dodecyl sulfate-polyacrylamide gel electrophoresis

AF:

angiogenic factor

TAF:

tumorderived angiogenic factor

CAM:

chorioallantoic membrane

EGF:

epidermal growth factor

NGF:

nerve growth factor

LDH:

lactate dehydrogenase

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Author notes

  1. J. F. Riordan (a member)

    Present address: Department of Biological Chemistry, Harvard Medical School, Boston, USA

  2. J. W. Fett & E. M. Alderman

    Present address: Department of Pathology, Harvard Medical School, Boston, USA

  3. J. L. Bethune

    Present address: Department of Radiology, Harvard Medical School, Boston, USA

Authors and Affiliations

  1. Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, 02115, Boston, Massachusetts, USA

    B. L. Vallee, J. F. Riordan (a member), N. Higachi, J. W. Fett, G. Crossley, R. Bühler, G. Budzik, K. Breddam, J. L. Bethune & E. M. Alderman

  2. Brigham and Women's Hospital, 250 Longwood Avenue, 02115, Boston, Massachusetts, USA

    B. L. Vallee, J. F. Riordan (a member), R. R. Lobb, N. Higachi, J. W. Fett, G. Crossley, R. Bühler, G. Budzik, K. Breddam, J. L. Bethune & E. M. Alderman

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Additional information

This work was supported by funds from the Monsanto Company under Agreements with Harward University and from the U.S. Public Health Service, Contract No. N01-CB-43942. We are particularly indebted to Bernard S. Wildi and Monte C. Throdahl for their advice, cooperation, and encouragement. We also thank Dr Judah Folkman for the initial supply of male mouse submaxillary glands and rat Walker carcinoma conditioned medium, for help with the CAM assays, assays in the rabbit cornea, and many helpful discussions; and R. Bretton, A. Ehrlich, B. Evans, F. Fu, N. Hay and B. Tsokanis for excellent technical assistance.

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Vallee, B.L., Riordan, J.F., Lobb, R.R. et al. Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review. Experientia 41, 1–15 (1985). https://doi.org/10.1007/BF02005853

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