The Pathogenesis of Metastasis

27 May

The overall pathogenesis of metastatic growth is a subject of concern to all individuals seeking a better understanding of the cause and control of cancer. It is usually the metastatic lesions of a primary neoplasm that are the direct or indirect cause of the demise of the patient with cancer. Since the first realization that metastatic neoplasia originated from a primary neoplasm (Chapter 1), the methods by which metastatic cells successfully colonize distant tissues have been investi- gated. Figure 10.11 is a diagram of the overall pathogenesis of metastatic lesions in a general sense.

Vascularization  of a primary neoplasm  involves an interesting  interaction  between neo- plastic cells and the host, the latter supplying the vasculature—a topic discussed in Chapter 18. Invasion into the vascular system occurs by mechanisms that have already been discussed (Fig- ure 10.8 and text). Neoplastic cells within the circulation interact with blood platelets, lympho- cytes, and other circulating blood cells of the host. Fibrinogen and fibrin, its polymeric product, are likely to be related in a second, indirect manner to the formation of metastases (Malone et al., 1979). The interaction  of neoplastic  cells with platelets during and after their “docking” (Figure 10.10) is also a critical  factor in the initial establishment  of a metastatic  clone. The “locking”  or subsequent  late phase of the process depicted in Figure 10.10 involves a firmer adhesion mediated by activation-dependent  integrins and potential interaction with blood coagu- lation elements,  especially  blood platelets.  Neoplastic  cells in vitro exhibit the capability  to cause platelet  aggregation,  which also involves  surface  carbohydrate-receptor  interactions (Honn et al., 1992). The combination of platelet interaction with the neoplastic cell to form a minithrombus and the interaction of integrins with surface molecules on the endothelial cell sta- bilize the interaction  of the neoplastic  cell with the endothelial  surface. Following  this, there

Figure 10.11 The pathogenesis  of metastasis.  Note that the extension  from the primary neoplasm  in- volves invasion into the vascular system and the subsequent development  of metastases through the dock- ing and locking mechanisms in Figure 10.10. (Adapted from Poste and Fidler, 1980, with permission of the authors and publishers.)

occurs both the release of proteases, as in the invasive process (Figure 10.8), as well as endothe- lial cell retraction to aid in the invasive process of the metastatic cell through the endothelial membrane.  Furthermore,  platelets release a variety of growth factors, including  the platelet- derived growth factor (PDGF) and transforming growth factor-β (TGF-β) (Chapter 16), which can enhance growth of the metastatic clone. Subsequent to extravasation or invasion through the blood vessel wall, subsequent growth of the metastatic clone depends on a variety of complex interactions between the neoplastic cell population and that of the host. Paramount among these interactions is the development of blood vessels (angiogenesis) from normal host cells to supply the vasculature,  oxygen, and nutrients to the developing neoplasm. This subject is considered more extensively as a complex host-tumor relationship in Chapter 18.

Random Posts

Comments are closed.