Relevance of microenvironmental pH for self-organized tumor growth and invasion.

The process of tumor cell growth, invasion and metastasis involves a self-organized cascade of multiple tumor-host and tumor-immune interactions. The prediction of cancer development based exclusively on molecular evidence is still impossible because of the complex and heterogeneous control mechanisms actually acting in cellular systems. In contrast, most tumor cell systems display a limited spectrum of macroscopically observable modes of action which emerge as a result of cellular self-organization. The stability of the dynamic modes is controlled by relatively few order parameters. Their number and characteristics are different in normal and neoplastic growth. A systems-oriented analysis utilizing our method of Structured Biological Modelling (SBM) suggests that microenvironmental pH (pHme) can function as an important order parameter for self-organized cancer development. In the scope of an integrated minimal model for the multistep development of invasive tumor growth, this finding will be discussed with respect to its evolution, diagnostic relevance and possible therapeutical implications. The study underlines the necessity of minimal invasive methods for the on-line in vitro and in vivo monitoring of pH, oxygen, signal transducing molecules and essential nutrients in the microenvironment of tumor cells.