Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Abstract

Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

Nonlinear Modeling and Simulation of Tumor Growth

“…This approach is expected to improve current cancer modeling efforts because a multiscale approach model connects previous work focused on specific scales and specific processes (e.g., single cell motion) by performing 3-dimensional simulations of in vivo tumors. This methodology further allows the possibility to see beyond the current reductionist picture of invasion and migration [78,111,187,198,204,117,206,64,179,75,77,53,172], with the goal to enable prediction of disease progression and treatment response based on patient-specific tumor characteristics. …”

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

“…Thus, the gene signature associated with poor prognosis facilitates the emergence of metastatic cells in the primary tumor, but the specific set of genes associated with bone metastasis seems responsible for the cellular activities necessary for metastatisation [6][7][8]. For completeness, the metastatic capacity might be considered as a late, acquired event in tumorigenesis and during secondary growth, through epigenetic control of transcription [9,10].…”

Increased cell survival, migration, invasion, and Akt expression in PTHrP-overexpressing LoVo colon cancer cell lines

“…As with other cancer cells, colon cancer invasion and metastasis requires that a cell acquire a motile phenotype to penetrate tissue and reach the vasculature and lymphatics [3,4]. Cancer cells also adopt survival mechanisms, thereby avoiding apoptosis [5].…”

“…Cancer cells also adopt survival mechanisms, thereby avoiding apoptosis [5]. These properties are dependent on inherent tumor cell characteristics [3,6,7], and on the presence of several growth factors in the metastatic microenvironment. One of these factors is parathyroid hormone-related protein (PTHrP).…”