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U N I T 1
Cell and Tissue Function
move through the degraded matrix and gain access to
a blood vessel. Once in the circulation, the tumor cells
are vulnerable to destruction by host immune cells.
Some tumor cells gain protection from the antitumor
host cells by aggregating and adhering to circulating
blood components, particularly platelets, to form tumor
emboli. Exit of the tumor cells from the circulation
involves adhesion to the vascular endothelium followed
by movement through the capillary wall into the site of
secondary tumor formation by mechanisms similar to
those involved in invasion.
Once in the distant site, the process of metastatic
tumor development depends on the establishment of
blood vessels and specific growth factors that promote
proliferation of the tumor cells. Tumor cells as well as
other cells in the microenvironment secrete factors that
enable the development of new blood vessels within
the tumor, a process termed
angiogenesis
(to be dis-
cussed).
11–13
The presence of stimulatory or inhibitory
growth factors correlates with the site-specific pattern
of metastasis. For example, a potent growth-stimulating
factor has been isolated from lung tissue, and stromal
cells in bone have been shown to produce a factor that
stimulates growth of prostatic cancer cells.
Recent evidence indicates that chemoattractant cyto-
kines called
chemokines
that regulate the trafficking of
leukocytes (white blood cells) and other cell types under
a variety of inflammatory and noninflammatory con-
ditions may play a critical role in cancer invasion and
metastasis.
14,15
Tumor cells have been shown to express
functional chemokine receptors, which can sustain cancer
cell proliferation, angiogenesis, and survival and promote
organ-specific localization of metastasis. Insights into the
presence and role of chemokines in cancer spread and
metastasis provide directions for development of future
diagnostic and treatment methods. The implications
include methods to diminish metastasis by blocking the
action of selected chemokines and/or their receptors.
Primary tumor
Platelets
Metastatic tumor
Metastatic subclone
Intravasation
Interaction with
lymphocytes
Tumor cell
embolus
Extravasation
Angiogenesis
FIGURE 7-5.
The pathogenesis of metastasis. (Adapted
from Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran
Pathologic Basis of Disease. 7th ed. Philadelphia, PA: Elsevier
Saunders; 2005:311.)
SUMMARY CONCEPTS
■■
The term neoplasm refers to an abnormal mass
of tissue in which the uncontrolled proliferation
of cells exceeds and is uncoordinated with that
of the normal tissues. Differentiation refers to the
extent to which neoplastic cells resemble their
normal counterparts.
■■
Neoplasms are commonly classified as being
either benign or malignant. Benign neoplasms
are well-differentiated tumors that resemble
their tissues of origin, but have lost the ability to
control cell proliferation.They grow by expansion,
are enclosed in a fibrous capsule, and do not
cause death unless their location is such that
it interrupts vital body functions. Malignant
neoplasms are less–well-differentiated tumors
that have lost the ability to control both cell
proliferation and differentiation.They grow in a
disorganized and uncontrolled manner, invade
surrounding tissues, have cells that break loose
and travel to distant sites to form metastases, and
inevitably cause suffering and death unless their
growth can be controlled through treatment.
■■
Anaplasia is the loss of cell differentiation in
cancerous tissue. Undifferentiated cancer cells
are marked by a number of morphologic changes,
referred to as pleomorphism.The characteristics
of altered proliferation and differentiation are
associated with a number of other changes
including genetic instability, growth factor
independence, loss of cell density–dependent
inhibition, loss of cohesiveness, and anchorage
dependence, faulty cell-to-cell communication,
an indefinite cell life span (immortality), and
expression of fetal antigens not produced by
their normal adult counterparts, and abnormal
production of hormones and substances that
affect body function.
■■
The rate of growth of cancerous tissue depends
on the ratio of dividing to resting cells (growth
fraction) and the time it takes for the total mass
of cells in the tumor to double (doubling time). A
tumor is usually undetectable until it has doubled
30 times and contains more than a billion cells.
