Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth

• Published in: Cancer research (Chicago, Ill.) Vol. 56; no. 4; pp. 921 - 924
• Main Authors: MELNYK, O, SHUMAN, M. A, JIN KIM, K
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.02.1996
• Subjects: Animals; Antibodies - pharmacology; Biological and medical sciences; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Carcinoma, Squamous Cell - pathology; Cell Line; Chloramphenicol O-Acetyltransferase - biosynthesis; Dissemination; Endothelial Growth Factors - immunology; Endothelial Growth Factors - physiology; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lymphokines - immunology; Lymphokines - physiology; Medical sciences; Mice; Mice, SCID; Neoplasm Metastasis; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Transfection; Tumor cell; Tumor Cells, Cultured; Tumors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Antineoplastic agent; Human; Squamous cell carcinoma; Angiogenic factor; Rodentia; Antimetastatic agent; Malignant tumor; Monoclonal antibody; Metastasis; Vertebrata; Experimental disease; Mammalia; Treatment; Mouse; Animal; Immunotherapy; Inhibition; Vascular endothelial growth factor; Growth factor
• ISSN: 0008-5472

Tumor growth is dependent on new blood vessel formation. Inhibition of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and angiogenic factor secreted by a variety of tumors and tumor cell lines, is sufficient to inhibit primary tumor growth. In the present study, we examined the effect of inhibiting VEGF on tumor cell micrometastasis. A transfectant of A431 (a human epidermoid carcinoma cell line) expressing chloramphenicol acetyltransferase (CAT) was injected s.c. into severe combined immunodeficiency (scid) mice, which were then sacrificed after 6 weeks. The presence of A431 metastases at distant sites was demonstrated by detection of CAT activity in whole-organ lysates. Treatment of animals with VEGF-neutralizing antibodies not only inhibited primary tumor growth but also suppressed metastases, as determined by CAT activity in organ lysates. In experiments to determine the mechanism by which anti-VEGF antibody inhibited metastasis, control animals were sacrificed when their tumors had reached the same size as tumors in VEGF antibody-treated animals. Metastases were uniformly present in these control animals. These findings show that inhibition of VEGF alone is sufficient to prevent tumor growth and dissemination in vivo. The inhibitory effect on metastases appears to be distinct from that on primary tumor growth.