Tumor tissues heterogeneity molecules

Fig. 1. Microenvironmental factors and the invasive process. The primary tumor is a heterogeneous mix of cell populations, further diversified by gradients of blood-borne nutrients, oxygen, and drugs. Hypoxia contributes to treatment resistance, upregulates pro-angiogenic and pro-invasive molecules, and helps to maintain cancer stem-like cell populations. Tumor cells may undergo epithelial-to-mesenchymal transition (EMT), enter blood vessels, and disseminate to distant sites where they extravasate, invade, and colonize the tissues. Once established, the cells may undergo the reverse program (mesen-chymal-to-epithelial transition, MET) and proliferate to form metastases, the major reason for treatment failure.

In addition to differences between tumors and their environment, the neo vascular phenotype itself may differ between tissues. A variety of vascular morphologies has been discussed above, and specific molecules expressed by the neovasculature may also vary. For example, binding of the antiangiogenic factor endostatin was found to almost all bladder tumor vessels, three quarters of the vessels in prostatic carcinomas, and only 11% of renal tumor vessels [63]. VEGFR3, which, in most tissues, is restricted to lymphatics, has been identified in the new blood vessels of inflamed synovium [26]. These and other characteristics of different neo vascular beds may contribute to heterogeneous responses to therapies that target the vasculature. 

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