Overexpression of laminin ?1 chain in colonic cancer cells induces an increase in tumor growth

Abstract

Laminins represent a growing family of glycoproteins constituting the basement membrane. They are known to direct many biological processes. With respect to carcinogenesis, laminins play an important role in cell adhesion, mitogenesis, differentiation and even metastasis. To further study the biological significance of laminin-1 (composed of ␣1, ␤1 and ␥1 chains) in intestinal cell differentiation or tumorigenesis, an ␣1-laminin expression vector was introduced into the HT29 colonic cancer cells, in which laminin ␣1 chain is not expressed. Upon transfection of the ␣1 chain, the ␣1␤1␥1 trimer was found secreted in the media along with free Key words: laminins; basement membrane; colonic cancer cells; tumor growth; differentiationIt is well established that in multicellular organisms, extracellular matrix molecules control various physiologic activities such as cell growth, migration, apoptosis and differentiation. The extracellular network includes the interstitial matrix and basement membranes. The basement membranes that separate the connective tissue from epithelia, muscle fibers, blood vessels and nerves are formed by a complex set of collagens and of noncollagenous glycoproteins such as laminins, nidogen and of proteoglycans, which have a unique composition in each organ. Laminins are multifunctional molecules forming a family of proteins that display organ, site and developmental specificity. 1,2 The first characterized laminin isoform, laminin-1 (composed of ␣1, ␤1 and ␥1 chains), is a crosslike-shaped molecule assembled into a triplestranded coiled-coil structure designated as the long arm. 3 As for the other extracellular matrix molecules, laminin-1 is made up of specific structural domains that allow self-assembly, permit interaction with other basement membrane molecules and encode information for the cells via specific transmembrane receptors, mostly of the integrin family. 4 Recent studies performed on various organs during development show that laminin-1 has a rather limited expression. 5 Despite such restricted expression, crucial roles for laminin-1 in organ development and in cell differentiation have been demonstrated by cell-coating experiments, blocking antibody and antisense strategies. Several major functions have been assigned to the constitutive ␣1 chain of laminin-1, among which are the polarization of developing kidney tubules, 6,7 lung alveolar formation, 8 development of submandibular glands 9 and polarization and functional differentiation of mammary and intestinal cells. 10,11 Conversely, alterations in cell-matrix and cell-cell interactions have been shown in a number of pathologic situations, such as inflammatory processes, wound healing and malignant transformation. In colorectal cancer, perturbations in the production, deposition and degradation of matrix molecules, among which are laminins, have been observed. [12][13][14][15][16] The role of laminin-1 in tumor growth and metastasis has been evaluated in several cell systems. In particular, it was shown that coinjection of puri...

Extracellular Matrix Remodeling by Human Granzyme B via Cleavage of Vitronectin, Fibronectin, and Laminin

“…Laminin-10 has been observed at the leading edge of colon cancers (37,59) and is known to induce cell spreading (including the presence of pseudopod-like extensions) and increase motility of LIM1215 cells in the presence of epidermal growth factor (58,60). Although GrB pretreatment of laminin-10 matrix had no effect on the initial adhesion of LIM1215 cells (data not shown), cell spreading was significantly inhibited in the presence of GrB (Fig.…”

Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

“…Loss of a well-defined basement membrane is one of the features of neoplastic proliferation for epithelialderived tumors. Laminin (LN), a major glycoprotein of BM which has been shown to regulate a variety of biological phenomena including cell attachment, growth, morphology, and cell migration by specific high affinity receptors, and plays an important role in the interaction of tumor cells with the BM, the differentiation, invasion and metastasis of tumors [26].…”

Molecular Analysis of Laminin N-terminal Domains Mediating Self-interactions

“…Laminins constitute the major noncollagenous protein component within the basement membrane and are crucial for its formation (1,2). Through their interactions with specific receptors, especially members of the ␤ 1 integrin family and ␣-dystroglycan, they induce many cellular effects, including differentiation and cellular and axonal migration.…”

“…These parts of the ␤ and ␥ chains each contain two globular domains, designated IV and VI, whereas there are three, IVa, IVb, and VI, in the short arm contributed by the ␣ chain. The globules are interspersed by multiple laminin epidermal growth factor-like (LE) 1 domains forming rods. The VI domains are also designated laminin N-terminal (LN) domains, and this nomenclature will be used throughout.…”