Devita, Hellman, and Rosenberg's Cancer

LWBK1006-02 LWW-Govindan-Review November 24, 2011 11:18

Chapter 2•Molecular Biology of Cancer Part 2 31

growth. Metastasis virulence genes confer protection to tumor cells in

the distant environment but confer no protection to the primary tumor.

Answer 2.37. The answer is C.

TAMs can comprise a large percentage of the bulk of a tumor mass.

Through secretion of FGF, EGF receptor ligands, and PDGF, they can

stimulate tumor cell growth and motility. Furthermore, by producing uPA,

MMP7, and MMP9, TAMs help degrade basement membrane allowing

tumor cells to invade and metastasize.

Answer 2.38. The answer is A.

Invasion starts with loss of cellular adhesion. This is largely mediated

by loss of E-cadherin, the prototypic protein of the cadherin family. Cad-

herins are transmembrane glycoproteins that mediate cellular attachment.

They anchor the cell through attachments to the actin cytoskeleton via

another family of proteins called the catenins.

Answer 2.39. The answer is D.

CTCs experience multiple stressors in the circulation, leading to a short

half-life. Of these, physical stressors such as shear forces or mechanical

injury may limit CTC life span. Also, EC-mediated stressors such as nitric

oxide may induce apoptosis in CTCs. DARC, a Duffy blood group glyco-

protein, interacts with KAI1 expressed on CTCs causing them to undergo

senescence.

Answer 2.40. The answer is C.

Ezrin links the cell membrane to the actin cytoskeleton and has been found

to assist in extravasation of CTCs via activation of the MAPK pathway.

VEGF has been shown to assist in CTC extravasation by causing disrup-

tions in EC junctions and increased vascular permeability. CTC expression

of CXCR4 interacts with CXCL12 expressed on certain organs, such as

lung, liver, bone, and lymph nodes, allows for selective extravasation.

Answer 2.41. The answer is B.

Breast, lung, and kidney cancer typically cause osteolytic lesions on metas-

tasizing to bone. Unlike these lesions, prostate cancer causes osteoblas-

tic lesions on metastases to bone. In contrast with osteolytic metastasis,

osteoblastic lesions result from the preferential stimulation of osteoblasts

or the inhibition of osteoclasts. This is mediated through many different

molecules, including bone morphogenetic proteins such as WNT, TGF-,

IGF, PDGF, FGF, and VEGF.

Answer 2.42. The answer is C.

Because of the microenvironment the liver provides and the dual blood

supply (from the portal vein and hepatic artery), the liver is a common

site of metastasis. Colon cancer generally seeds the liver via the portal

system, whereas breast, lung, and melanoma approach the liver via the

systemic circulation through the hepatic artery.