Invasion And Metastasis As Multistep Processes

Even more than tumor expansion as such, the extent of local invasion and distant metastasis determine the clinical outcome of cancers, especially in solid cancers like carcinomas. Invasion and metastasis can be regarded as multistep processes, where invasion towards a certain stage constitutes a prerequisite for metastasis. Each step requires and selects for certain properties of the tumor cells. Therefore, overall, metastasis may be a very inefficient process. While details vary, invasion and metastasis of a carcinoma in general can be roughly described by the following sequence of steps (Figure 9.1):

(1) While the carcinoma proliferates and extends laterally and vertically within the epithelium, the tumor cells become less adherent to each other and to adjacent normal epithelial cells.

(2) The underlying stroma becomes activated and inflammation may occur. The basement membrane which separates the epithelium from the underlying mesenchymal connective tissue is partly or completely destroyed.

Intraepithelial Growth

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