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Cell-cell adhesion in invasion and metastasis of carcinomas

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Mammary Tumorigenesis and Malignant Progression

Part of the book series: Cancer Treatment and Research ((CTAR,volume 71))

Abstract

Metastasis of tumor cells involves a series of consecutive attachment and deattachment events that are based on a multitude of specific cell-to-cell and cell-to-substrate interactions. The process is initiated by disaggregation of invasive cells from the primary carcinoma — a step that requires a breakdown of intercellular adhesion (see below for a detailed discussion). Invasion then depends on novel adhesive interactions with extracellular matrix components of the basement membrane and the mesenchymal tissue. The hallmark of invasion (in particular in carcinomas) is the penetration of tumor cells through the surrounding basement membrane — a process that indicates the transition from a benign carcinoma in situ to a malignant invasive tumor. This step requires adhesion to and digestion of extracellular matrix molecules, like laminin and collagen type IV. It has been shown, for instance, that invasive tumor cells express elevated levels of type IV collagenase and of both laminin and collagen IV receptors [1,2]. A similar combination of changes in proteolytic and adhesive activities also aids the invasive cells in their movement through the interstitial stroma and through basement membranes of blood vessels. For instance, metastasis formation in vivo could be suppressed by injection of the cell attachment peptide YIGSR that is located in the laminin Bl chain [3]. Various experiments have shown that proteins containing the RGD amino acid sequence for recognition by integrin receptors serve as substrates for migrating malignant cells [4–6]. An important role of integrin receptors in metastasis formation was revealed by expression of the α2 integrin cDNA in low metastatic rhabdomyosarcoma cells. The transfected cells expressed functional α2β1 adhesion receptors, they exhibited enhanced adhesion to collagen and laminin in vitro, and they produced more metastatic tumor colonies in nude mice in comparison to the parental cells [7]. Interestingly, transformation of rodent cells by oncogenic viruses resulted in a decrease of integrin receptors [8], and overexpression of the a5βl integrin in transformed Chinese hamster ovary cells reduced tumorigenicity and motility of the cells [9]. These results reveal a dual role of cell matrix adhesion in tumorigenesis: on the one hand, adhesion to extracellular matrix is required for cell locomotion, but on the other hand, it can impose constraints on motility and growth and thus must be minimized in certain cases [10].

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  1. Jürgen Behrens
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  2. Walter Birchmeier
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Editors and Affiliations

  1. Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC, USA

    Robert B. Dickson  & Marc E. Lippman  & 

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Behrens, J., Birchmeier, W. (1994). Cell-cell adhesion in invasion and metastasis of carcinomas. In: Dickson, R.B., Lippman, M.E. (eds) Mammary Tumorigenesis and Malignant Progression. Cancer Treatment and Research, vol 71. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2592-9_13

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  • DOI: https://doi.org/10.1007/978-1-4615-2592-9_13

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