Mini-reviewLaminin-induced signaling in tumor cells
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.