Shark Cartilage Contains Inhibitors
of Tumor Angiogenesis
Inhibition of Tumor Angiogenesis Mediated
TUMOR ANGIOGENESIS MEDIATED
Brem and Judah Folkman
(From the Department of Surgery, Children's Hospital Medical Center,
Harvard Medical School, Boston, Massachusetts 02115)
We have previously suggested that solid tumor growth is not continuous,
but may be separated into two stages, avascular and vascular (1, 2). In
the avascular phase, spheroidal tumors cannot generally exceed a diameter
of 1-2 mm or a population of more than 101, cells (3, 4). Further growth
occurs after new capillaries have been elicited from the host, and have
penetrated the tumor.
Tumors elicit these new capillaries from the host by releasing a diffusible
material, which we have termed tumor-angiogenesis-factor (TAP),' which
is mitogenic to capillary endothelial cells (5-8).
Under the usual conditions of transplanting experimental tumors, the
avascular phase is brief; i.e. 3-5 days (5). However, under special conditions,
the avascular phase can be prolonged and tumors then become dormant. For
example, when tumors are suspended in the anterior chamber of the rabbit
eye, new vessels cannot reach them, and the tumors stop growing at about
I mm diameter, although they remain viable (3).
We have suggested that if a means could be found to inhibit TAF, or
block its stimulatory effect upon capillaries, tumors might be held in
the avascular phase (9,10). We now show that cartilage from newborn rabbits
strongly inhibits capillary proliferation induced by tumors. The data suggests
that this inhibition may be mediated by a diffusible factor, thereby preventing
these tumors from progressing to the vascular phase.
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