Tumor Invasion and Metastasis

Tumor Invasion And Metastasis



Tumor Invasion and Metastasis

1) Discuss the mechanisms involved in tumour invasion and metastasis?

Many studies in experimental systems but also in human patients have revealed that alterations in the adhesive properties of tumor cells correlate with progression to tumor malignancy. In fact, an increasing body of evidence now indicates that an aberrant tumor cell adhesion is causally involved in tumor progression and metastasis, rather than merely being a consequence of it.

2) Discuss the mechanisms of carcinogenesis

In particular, tumor invasion and metastasis, both hallmarks of tumor malignancy, frequently coincide with the loss of E-cadherin-mediated cell-cell adhesion. Expression of E-cadherin, the most abundant adhesion molecule in adherens junctions of epithelia, is downregulated in most, if not all, epithelial cancers (Birchmeier, 1994, 11-26). This observation, led to the hypothesis that the loss of intercellular contacts would generate permissive conditions for tumor cell migration . Indeed, several research groups have shown that reconstitution of a functional E-cadherin adhesion complex suppresses the invasive phenotype of many different tumor cell types.

Of course, the dual role of ß-catenin in cell adhesion and Wnt-signaling poses a number of questions relevant for carcinogenesis. For example, is E-cadherin dominant over the Wnt-signaling pathway by sequestering ß-catenin, or in other words, is the loss of E-cadherin a prerequisite for the Wnt-signaling pathway to be active? If this were the case, the loss of E-cadherin function may promote Wnt-dependent activation of ß-catenin and, hence, directly affect the transcriptional program of tumor cells.

3) Describe the gross(naked eye) and microscopic characteristics of benign and a malignant tumor

Although E-cadherin has been the most extensively studied cadherin in the context of tumor biology, recent studies highlighted the role of other members of the cadherin family in tumor cell migration and invasion (Vleminckx, 1991, 107-119). N-cadherin, in particular, enhances cell motility of various tumor cell types, in some cases even overcoming E-cadherin-dependent cell-cell adhesion . In addition, de novo expression of N-cadherin in tumor cells which have lost functional E-cadherin has been repeatedly reported.

4) Define melanoma and describe its different types. How can you differentiate between melanoma and moles?

These data raise the intriguing possibility that a 'cadherin switch' from pro-adhesive, epithelial cadherins (e.g. E-cadherin) to mesenchymal, pro-migratory cadherins (e.g. N-cadherin and cadherin-11) promotes tumor invasion and metastasis . It remains to be clarified if (and how) de novo expression of N-cadherin directly causes the downregulation of E-cadherin during tumor progression, as indicated by studies with carcinoma cells in culture (Birchmeier, 1994, 11-26). Moreover, it is conceivable that a change in cadherin repertoire results in a change of neighbors, for example by supporting the interaction of tumor cells with the stroma. Thus far, a statistical correlation between the cadherin switch and tumor progression in vivo has been shown in patients with melanoma and with prostate carcinoma . Future studies involving human tumor specimens as well as in mouse tumor models should help to assess whether different cadherins are engaged in a cadherin switch in different tumor ...