Cancer Letters

Cancer Letters

Volume 223, Issue 1, 1 June 2005, Pages 1-10
Cancer Letters

Mini-review
Laminin-induced signaling in tumor cells

https://doi.org/10.1016/j.canlet.2004.08.030Get rights and content

Abstract

Laminin is the main non-collagenous glycoprotein found in the basement membrane. The various laminin isoforms are involved in many physiological and pathological processes, including cancer dissemination. The interaction of cancer cells with laminin was identified as a key event in tumor invasion and metastasis. Laminin effects are mediated by laminin receptors that are divided into two groups: integrin and non-integrin receptors. Activation of a specific signal transduction pathway in the cell depends on various factors and may be altered when normal tissue becomes neoplastic. Laminin signals via multiple signal transduction pathways involving various components such as G-proteins, intracellular calcium, phospholipase D, mitogen activated protein kinases, phosphatases, focal adhesion kinase, small GTPases of the Rho family, and cytoskeleton components. This review focuses on the role of laminin in tumor progression, its signaling via the non-integrin 67 kDa laminin receptor and via integrins and the reciprocal relations between these receptors in certain tumors.

Section snippets

Laminin

Laminin is the main non-collagenous glycoprotein found in the basement membrane [1]. It is a heterotrimer of three subunits, α, β and γ held together by disulphide bonds to form a shape of a cross [2], [3], [4]. Five α chains, three β chains and three γ chains have been identified and by combination they assemble to form over 14 laminin isoforms [5] that have different tissue distributions and development functions [2], [4] (Table 1 [5], [6]). Laminin is the first basement membrane component

Laminin promotes tumor progression

Metastatic spread of cancer continues to be the greatest challenge to cancer cure. At the core of the process lie the changing adhesive preferences of the tumor cells, which determine their interactions with other cells and with the extracellular matrices, mainly in attachment and degradation processes [3], [20], [21]. Basement membranes are lost or penetrated by tumor cells during invasion and metastasis, and discontinuities were shown in basement membranes of malignant tumors but not in those

Laminin signaling

It appears that laminin activates various signal transduction pathways. It was shown that chemotaxis induced by laminin-1 is sensitive to pertussis toxin, indicating the involvement of pertussis toxin-sensitive G protein in the signals initiating motility to soluble laminin-1. The absence of response to pertussis toxin indicates that a distinct signal transduction pathway may be involved in haptotaxis [17]. It was shown that human osteoclast-like cells selectively recognize laminin isoforms, an

Laminin receptors

The biological effects of laminin are mediated by laminin receptors that are divided into two major groups: integrin and non-integrin receptors (Table 2) [5], [21], [36], [37], [38], [39]. Insufficient data exist regarding the roles of both families of receptors in mediating the various effects of laminin [2], [23].

Summary

The interaction of cancer cells with laminin is a key-event in tumor invasion and metastasis. Laminin effects are mediated by laminin receptors, and receptor expression is altered in cancer. Activation of a specific signal transduction pathway in the cell depends on the laminin isoforms the cell binds to, the conformation of the glycoprotein, the duration of exposure to laminin and the expression pattern of the different laminin receptors. All the above factors may be altered when normal tissue

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    1

    The work of Vered Givant-Horwitz is supported by the Yeshaya Horowitz Fellowship grant.

    2

    Reuven Reich is affiliated with the David R. Bloom Center of Pharmacy at the Hebrew University.

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