Pathophysiological Basis for the Formation of the Tumor Microenvironment

Abstract

Poor microenvironmental conditions are a characteristic feature of solid tumors. Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing tumor mass. Regions of low oxygenation (hypoxia) is believed to be the most critical deficiency, since it has been well documented to play a significant role in influencing the response to conventional radiation and chemotherapy treatments, as well as influencing malignant progression in terms of aggressive growth and recurrence of the primary tumor and its metastatic spread. As a result, significant emphasis has been placed on finding clinically applicable approaches to identify those tumors that contain hypoxia and realistic methods to target this hypoxia. However, most studies consider hypoxia as a single entity, yet we now know that it is multifactorial. Furthermore, hypoxia is often associated with other microenvironmental parameters, such as elevated interstitial fluid pressure, glycolysis, low pH, and reduced bioenergetic status, and these can also influence the effects of hypoxia. Here, we review the various aspects of hypoxia, but also discuss the role of the other microenvironmental parameters associated with hypoxia.

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“…Chromosome X gains were observed in neoplastic transformation of male epithelial cells [28], whereas epigenetic instability/loss of inactive X chromosome frequently occurs in female basal breast cancer cases [29]. Similarly to other solid tumors, basal like tumors demonstrate heterogeneity of their tumoral microenviroment, including intratumoral level of oxygen, nutrient and pH [30,31].…”

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“…At this point, the tumor requires new tumor-specific blood vessels, which are formed primarily from the host vasculature via angiogenesis (2). The tumor neovasculature that results is very different from vessels found in normal tissues (3,4): it is structurally chaotic with abnormal vascular density, contour irregularities, haphazard vessel interconnection, and loss of hierarchy. The tumor blood vessels are very primitive, with incomplete or missing basement membranes, and lack innervation and pharmacological receptors.…”

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