Growth and Other Characteristics of TUmors 21 Introduction to Tumors

A tumor starts with a single or a couple of mutated cancerous cells surrounded by healthy, normal tissue. As the cancerous cells replicate, due to its modified DNA, it generally develops at a higher speed than normal cells. The earliest detectable malignant lesions are often referred to as in situ cancers. These are small tumors (a few millimeters in diameter) localized in tissues. At this stage, the tumor is usually avascular, i.e., lacking its own network of blood vessels to supply oxygen and nutrients (Ruddon 1987). Nutrients are provided primarily by diffusion resulting in a slow growth of the tumor. As the cancerous cells develop further, surrounding tissue will not be able to compete for nutrition due to a limited supply of blood. Due to the insufficient nutrient supply, some tumor cells perish, especially those located inside the tumors. Compared to tumor cells at the edge of the tumor, these cells rely solely on diffusion to receive nutrients and to eliminate waste products. The cancerous cells will continue to duplicate and displace surrounding healthy cells until they reach a diffusion-limited maximal size where the rate of tumor proliferation is equal to the rate of tumor cell death. Unless a better connection with the circulatory system is created, tumors cannot grow beyond this diffusion-limited maximal size which is around 2 mm in most tumors (Grossfeld et al. 2002; Jones and Harris 1998). Tumors stay in this stage for years until they initiate the formation of blood vessels (called angiogenesis).

In order to continue growing, tumors need to be vascularized and vascularization of tumors is stimulated by angiogenesis factors (such as vascular endothelial growth factor (VEGF) family, transforming growth factor b, ephrins, cadherin 5-type 2, etc.). The vascularized tumors begin to grow more as nutrition supply is established. Clinically detectable tumors (approximately 109 cells, about 1 g mass) may be achieved within a few months or years, depending on cell type. By that time, the tumor will have already gone through approximately two thirds of its lifetime, with about a 30 cell population doubling. If the tumor is unchecked, five more population doublings would produce a cancer mass of about 32 g, five more doublings would give a 1 kg mass tumor of approximately 1012 cells. The tumor mass compresses surrounding tissues, invades basement membranes, and metasta-sizes (Ruddon 1987). This exponential growth of tumors and their metastasis characteristics are the reasons why early cancer detection is of extreme importance.

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