Summary
All malignant tumors shed cells into the circulation. The number of circulating tumor cells bears no relation to the extent of secondary growth. This is determined by the number of tumor cells that cross the vessel wall and implant in extravascular sites. The rate of cellular emigration is regulated by the permeability of vessels harbouring tumor emboli, permeability in turn being dependent on the amount of alpha, 2, macro-globulin (AMG) lining vascular endothelium.
Agents which inactivate or digest AMG, e.g. proteases, have been shown to promote the dissemination of tumor. Some tumors secrete large amounts of proteases. These enzymes are believed to lyse the AMG laver and so to facilitate the emigration of tumor cells.
On this hypothesis, inhibitors of such proteases would have anti-metastatic properties. Present experiments lend support to this view. The proteinase inhibitor Trasylol, when allowed to act on tumor cells, has been shown to impair their capacity of setting up haematogenous metastases. It does not affect their viability or transplantability.
It is suggested therefore, that blood-borne tumor dissemination might be inhibited by perfusing the (primary) tumor bed with proteinase inhibitor, possibly in association with AMG.
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References
Ablin JR (1977) Immunobiology of the Prostate. Urologic Pathology. Tannenbaum M (ed) Lea and Febiger, Philadelphia 33–98
Barker CF, Billingham RE (1973) Skeletal muscle as privileged site for orthoptic skin allografts. J Exp Med 138:289–299
Becker CG, Harpel PC (1976) Alpha, 2, macroglobulin on human vascular endothelium. J Exp Med 144:1–9
Boeryd B, Hagman B, Johnson G, Ryd W (1975) Alteration of metastasis distribution by vasodilatory drugs. Pathol Eur 10:197–201
Coman DR (1953) Mechanisms responsible for the origin and distribution of blood borne tumour metastasis. A review. Cancer Res 13:397–404
De Bruyn PH, Yongoch C (1979) Entry of metastatic malignant cells into the circulation from a subcutaneously growing myelogenous tumor. J Nat Cancer Inst 62:1221–1227
Deckers PJ, Davis RC, Mannick, JA Tumor size and concomitant tumor immunity. Surg Forum 23:112–114
Fidler IJ, Gersten DM, Riggs CW (1977) Relationship of host immunity status to tumor cell arrest, distribution and survival in experimental metastasis. Cancer 40:46–55
Giraldi T, Kapitan M, Sava, G (1977) Antimetastatic effect of leucocyte intracellular inhibitor of neutral proteases. Cancer Res 37:3834–3835
Hover T, Mosher D, Vaheri A (1978) Cultured human monocytes synthesize and secrete alpha, 2, macroglobulin J Exp Med 145:1580–1589
Proctor JW, Rudenstam M, Alexander P (1973) A factor preventing the development of lung metastases in rats with sarcomas. Nature 242:29–31
Schmähl D, Rieseberg T (1958) Experimentelle Untersuchung in Ratten über die Metastasierung von Tumoren. Z Krebsforsch 62:456–480
Stein-Werblowsky R (1974) Skeletal muscle and tumor metastasis. Experientia 30:423–424
Stein-Werblowsky R (1978a) On the etiology of cancer of the prostate. Eur Urol 4:370–373
Stein-Werblowsky R (1978b) On the latency of tumor cells. Br J Exp Pathol 59:386–389
Stein-Werblowsky R (1978c) Vascular permeability in malignant disease. Experienta 34:404–405
Stein-Werblowsky R (1978d) On the lymphatic spread of cancer. Experientia 34:1340–1341
Sugarbaker EV, Ketcham AS (1977) Mechanisms and prevention of cancer dissemination. An overview. Sem Oncol 4:19–32
Thomson AV, Pugh Humphreys RGP, Horne CHW, Tweedie DJ (1977) Apronitin and Growth of Walker 256 carcinosarcoma in the rat. Br J Cancer 35:454–460
Thorgeirsson S, Lazzarini Robertson A (1978) The vascular endothelium. Am J Pathol 93:803–848
Vaage J (1978) In vivo and in vitro lysis of mouse cancer cells by antimetastatic effectors in normal plasma. Cancer Imm Immunother 4:457–461
Van de Velde C, Carr L (1977) Lymphatic invasion and metastasis. Experientia 33:837–843
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Stein-Werblowsky, R. On the prevention of haematogenous tumor metastases in rats the role of the proteinase inhibitor “Trasylol”. J Cancer Res Clin Oncol 97, 129–135 (1980). https://doi.org/10.1007/BF00409898
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DOI: https://doi.org/10.1007/BF00409898