LWBK1006-02 LWW-Govindan-Review November 24, 2011 11:18
Chapter 2•Molecular Biology of Cancer Part 2 29causing a focal degradation of a venule’s basement membrane. This is
likely a consequence of various proangiogenic growth factors secreted by
the tumor cell population or reactive stromal cells.Answer 2.25. The answer is D.
The single layer of periendothelial smooth muscle cells is formed by per-
icytes. These cells modulate EC function and are critical for the devel-
opment of a mature vessel network. In addition to regulation of vessel
diameter and permeability, they provide mechanical support and survival
of ECs through paracrine signaling. Because of their ability to maintain
EC survival, they have become an important target for antiangiogenic
therapy and it is hypothesized that they may mediate resistance to this
therapy.Answer 2.26. The answer is C.
The vasculature of solid tumors has several notable abnormalities. These
vessels are classically much dilated with little to no basement membrane
and have excessive tortuosity. A decreased number of pericytes portrays
a relative lack of support and excessive vascular leakiness. These features
contribute to the highly heterogeneous and often sluggish flow through
solid tumors and create areas of relative nutrient deprivation and hypoxia.
The increased leak from these vessels also allows for extravasation of high-
molecular-weight plasma proteins, leading to areas of elevated interstitial
fluid pressures.Answer 2.27. The answer is D.
VEGF promotes tumor angiogenesis is various ways, including stimula-
tion of EC division, inducing EC locomotion/migration, enhancing EC
survival by upregulating various inhibitors of apoptosis, and mobilizing
endothelial progenitor cells from the bone marrow to sites of angiogenesis.
Further, VEGF is approximately 50,000 times more potent than histamine
in increasing vascular permeability. VEGF is expressed in most if not all
of human cancers, and increased levels carry a poor prognosis.Answer 2.28. The answer is D.
There are at least four proposed mechanisms of how VEGF may pro-
mote tumor angiogenesis. VEGF can stimulate EC division, induce EC
locomotion/migration, and enhance EC survival by upregulating differ-
ent inhibitors of apoptosis and mobilizing endothelial progenitor cells
from the bone marrow to sites of angiogenesis. The necessary break-
down of the basement membrane of a parental venule is most likely
mediated by proangiogenic growth factors secreted by the tumor cells
themselves.Answer 2.29. The answer is A.
H1F1is upregulated by hypoxia. H1F1then, in turn, activates numer-
ous other genes, of which VEGF may be the most important.