Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner

Abstract

To date, cancer is still the second most prevalent cause of death after cardiovascular diseases in the industrialized word, whereby the primary cause of cancer is not attributed to primary tumor formation, but rather to the growth of metastases at distant organ sites. For several years it was considered that the well-known phenomenon of organ-specific spreading of tumor cells is mostly a mechanical process either directed passively due to size constraints (mechanical trapping theory) or due to a fertile environment provided by the organ in which tumor cells can proliferate (seed and soil hypothesis). Both mechanisms strongly depend on the adhesive properties of tumor cells either to endothelial cells and/or cancer cells, which are facilitated by a variety of cell adhesion molecules including carbohydrates and integrins. Within the past years it became evident that the organ-specific metastatic spreading of tumor cells does not only rely on heterotypic and homotypic adhesive interactions, but also on the interplay of chemokines and their appropriate receptors. Moreover, the identification of cancer stem cells in various tumor tissues has opened new questions. Cancer stem cells possess self-renewal, differentiation, and tumor-initiating capacities. Thus these cells are ideal candidates to be the seed of a secondary tumor. In the present review we will give a brief overview about the complex process of organ-specific metastasis formation depending on the interplay of adhesion molecules, chemokines, and the putative role of cancer stem cells in metastasis formation.

Analysis of Cell Migration within a Three-dimensional Collagen Matrix

“…We have recently demonstrated that hybrid cells, which derived from spontaneous fusion events between a human breast epithelial cell line and a human breast cancer cell line, but not the parental cells, responded to the chemokine CCL21 with an increased migratory activity 26 . CCL21 has been associated with lymph node metastasis formation of various cancer types, including breast 38 , suggesting that cell fusion could be a process how tumor (hybrid) cells could acquire metastatic properties 39,40 .…”

1997-2012: Fifteen Years of Research on Peptide Lunasin

“…The Arg-Gly-Asp motif present in the lunasin structure is a recognition site for integrin receptors present in the extracellular matrix (ECM). Integrins are heterodimeric receptors associated with cell adhesion, and cancer metastasis [62]. Treatment of KM12L4 cells with lunasin resulted in the modification on the expression of 62 genes associated with ECM and cell adhesion [59].…”

Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone

“…Chemokines are chemoattractant molecules that regulate cellular trafficking (1)(2)(3)(4). Secretion of chemokines by tumor cells has been correlated with angiogenesis, tumor growth and metastasis in a variety of experimental and human tumors (reviewed in refs.…”

“…Secretion of chemokines by tumor cells has been correlated with angiogenesis, tumor growth and metastasis in a variety of experimental and human tumors (reviewed in refs. 1,5). The organotropism of cancer metastasis is believed to occur, at least in part, through secretion of chemokines by distant organs/tissues that direct the migration of tumor cells that come into proximity to the tissue (1,5).…”

“…1,5). The organotropism of cancer metastasis is believed to occur, at least in part, through secretion of chemokines by distant organs/tissues that direct the migration of tumor cells that come into proximity to the tissue (1,5). SDF-1 (stromal cell derived factor-1) is a chemoattractant for hematopoietic cells to the bone marrow.…”