Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

U N I T 1

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

Metastatic subclone

Intravasation

SUMMARY CONCEPTS

Tumor cell embolus

■■ 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.

Platelets

Interaction with lymphocytes

Extravasation

Metastatic tumor

Angiogenesis

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 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.)