Summary
Expression of the 37-kDa laminin binding protein (37LBP/p40), a precursor of the 67-kDa laminin receptor, is well-correlated with the biological aggressiveness of cancer cells. To elucidate the direct role played by 37LBP/p40 in cancer cells, a murine lung cancer cell line T11, the 37LBP/p40 expression of which was remarkably diminished, was established by the introduction of the antisense 37LBP/p40-RNA using a retroviral vector. As a result, the population doubling time of T11 was prolonged (60 h) compared with that of P29, the non-transfected parental cell line (42 h), and TN2, a transfectant with vehicle only (40 h). In-vitro studies also showed that T11 cells adhered to immobilized laminin less firmly than P29 cells did. When 5 × 105 cells were subcutaneously inoculated into syngenic mice, the mean survival time of T11-recipients (77.0 ± 14.8 days) was also significantly prolonged compared with that for P29 (34.8 ± 5.5 days) and TN2 (36.7 ± 6.1 days) recipients (P < 0.001). The electron-microscopic view of the tumour tissue revealed that T11 cells were loosely apposed and their intercellular space was markedly widened. Some of the T11 cells sporadically degenerated with the infiltration of lymphocytes and neutrophils. These results suggest that the suppressed expression of 37LBP/p40 reduces the capability of lung cancer cell proliferation in vitro and tumour formation in vivo.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Auth, D. & Brawerman, G. (1992). A 33-kDa polypeptide with homology to the laminin receptor: component of translation machinery. Proc Natl Acad Sci USA 89: 4368–4372.
Beck, E., Ludwig, G., Auerswald, E. A., Reiss, B. & Challer, H. (1982). Nucleotide sequence and exact localization of the neomycin phosphotransferase gene from transposon Tn5. Gene 19: 327–336.
Carver, W., Molano, I., Reaves, T. A., Borg, T. K. & Terracio, L. (1995). Role of the alpha 1 beta 1 integrin complex in collagen gel contraction in vitro by fibroblasts. J Cell Physiol 165: 425–437.
Castronovo, V., Taraboletti, G. & Sobel, M. E. (1991a). Functional domains of the 67-kDa laminin receptor precursor. J Biol Chem 266: 20440–20446.
Castronovo, V., Claysmith, A. P., Barker, K. T., Cioce, V., Krutzsch, H. C. & Sobel, M. E. (1991b). Biosynthesis of the 67 kDa high affinity laminin receptor. Biochem Biophys Res Commun 177: 177–183.
Castronovo, V., Taraboletti, G. & Sobel, M. E. (1991c). Laminin receptor complementary DNA-deduced synthetic peptide inhibits cancer cell attachment to endothelium. Cancer Res 51: 5672–5678.
Castronovo, V., Campo, E., vanden Brule, F. A., Claysmith, A. P., Cioce, V., Liu, F. T., Fernandez, P. L. & Sobel, M. E. (1992). Inverse modulation of steady-state messenger RNA levels of two non-integrin laminin binding proteins in human colon carcinoma. J Natl Cancer Inst 84: 1161–1169.
Davis, S. C., Tzagoloff, A. & Ellis, S. R. (1992). Characterization of a yeast mitochondrial ribosomal protein structurally related to the mammalian 68-kDa high affinity laminin receptor. J Biol Chem 267: 5508–5514.
Demianova, M., Formosa, T. G. & Ellis, S. R. (1996). Yeast proteins related to the p40/laminin receptor precursor are essential components of the 40S ribosomal subunit. J Biol Chem 281: 11383–11391.
Eglitis, M. A., Kantoff, P., Gilboa, E. & Anderson, W. F. (1985). Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science 230: 1395–1398.
Ferrarini, M., Pupa, S. M., Zocchi, M. R., Rugarli, C. & Menard, S. (1994). Distinct pattern of HSP72 and monomeric laminin receptor expression in human lung cancers infiltrated by gamma/delta T lymphocytes. Int J Cancer 57: 486–490.
Gasparini, G., Barbareschi, M., Boracchi, P., Bevilazqua, P., Verderio, P., Dalla Palma, P. & Menard, S. (1995). 67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer. Int J Cancer 60: 604–610.
Graf, J., Ogle, R. C., Robey, F. A., Sasaki, M., Martin, G. R., Yamada, Y. & Kleinman, H. K. (1987). A pentapeptide from the laminin B1 chain mediates cell adhesion and binds the 67 000 laminin receptor. Biochemistry 26: 6896–6900.
Hunt, G. (1989). The role of laminin in cancer invasion and metastasis. Exp Cell Biol 57: 165–176.
Iwamoto, Y., Robey, F. A., Graf, J., Sasaki, M., Kleinman, H. K., Yamada, Y. & Martin, G. R. (1987). YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science 238: 1132–1134.
Iwamono, Y., Nomizu, M., Ymamada, Y., Ito, Y., Tanaka, K. & Sugioka, Y. (1996). Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr–Ile– Gly–Ser–Arg (YIGSR). Br J Cancer 73: 589–595.
Jackets, P., Minoletti, J., Belotti, K., Clausse, N., Sozzi, G., Sobel, M. E. & Castronovo, V. (1996). Isolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LPR/p40 at chromosome 3p21.3. Oncogene 13: 495–503.
Karp, J. E. & Broder, S. (1995). Molecular foundations of cancer: new targets for intervention. Nat Med 1: 309–320.
Keely, P. J., Fong, A. M., Zutter, M. M. & Santoro, S. A. (1995). Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha2 integrin mRNA in mammary cells. J Cell Sci 108: 595–607.
Kim, W., Lee, B. L., Jun, S. H., Song, S. Y. & Kleinman, H. K. (1998). Expression of 32-67-kDa laminin receptor in laminin adhesion-selected human colon cancer cell lines. Br J Cancer 77: 15–20.
Krieg, A. M., Gause, W. C., Gourley, M. F. & Steinberg, A. D. (1989). A role for endogenous retroviral sequences in the regulation of lymphocyte activation. J Immunol 143: 2448–2451.
Krieg, A. M., Yi, A. K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A. & Klinman, D. M. (1995). CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 54: 446–549.
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.
Landowski, T. H., Uthayakumar, S. & Starkey, J. R. (1995). Control pathways of the 67 kDa laminin binding protein: surface expression and activity of a new ligand binding domain. Clin Exp Metastasis 13: 357–372.
Magnifico, A., Tagliabue, E., Buto, S., Ardini, E., Castronovo, V., Colnaghi, M. I. & Menard, S. (1996). Peptide G, containing the binding site of the 67-kDa laminin receptor, increases and stabilized laminin binding to cancer cells. J Biol Chem 271: 31179–31184.
McCaffery, P., Neve, R. L. & Draeger, U. C. (1990). A dorso-ventral asymmetry in the embryonic retina defined by protein conformation. Proc Natl Acad Sci USA 87: 8570–8574.
Menard, S., Squicciarini, P., Luini, A., Sacchini, V., Rovini, D., Tagliabue, E., Veronesi, P., Salvadori, B., Veronesi, U. & Colnaghi, M. I. (1994). Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features. Br J Cancer 69: 1126–1129.
Mercurio, A. M. & Shaw, L. M. (1991). Laminin binding protein. BioEssays 13: 469–473.
Miller, A. D., Law, M. F. & Verma, I. M. (1985). Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol 5: 431–437.
Nakanishi, H., Takenaga, K., Oguri, K., Yoshida, A. & Okayama, M. (1992). Morphological characteristics of tumours formed by Lewis lung carcinoma-derived cloned cell lines with different metastatic potentials: structural differences in their basement membranes formed in vivo. Virchows Archiv A 420: 163–170.
Pasqualini, R., Koivunen, E. & Ruoslahti, E. (1997). αv integrins as receptors for tumor targeting by circulating ligands. Nature Biotechol 15: 542–546.
Pellegrini, R., Martignone, S., Menard, S. & Colnaghi, M. I. (1994). Laminin receptor expression and function in small-cell lung carcinoma. Int J Cancer, (suppl) 8: 116–120.
Rao, C. N., Castronovo, V., Schmitt, M. C., Wewer, U. M., Claysmith, A. P., Liotta, L. A. & Sobel, M. E. (1989). Evidence for a precursor of the high-affinity metastasis- associated murine laminin receptor. Biochemistry 28: 7476–7486.
Rieger, R., Edenhofer, F., Lasmezas, C. I. & Weiss, S. (1997). The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat Med 3: 1383–1388.
Robinson, M. O. & Simon, M. I. (1991). Determining transcript number using the polymerase chain reaction: Pgk-2, mP2, and PGK-2 transgene mRNA levels during spermatogenesis. Nucleic Acids Res 19: 1557–1562.
Saiki, I., Murata, J., Ikda, J., Sakurai, T., Nishi, N., Matsuno, K. & Azuma, I. (1989). Antimetastatic effects of synthetic polypeptides containing repeated structures of the cell adhesive Arg–Gly–Asp (RGD) and Tyr–Ile–Gly–Ser–Arg (YIGSR) sequences. Br J Cancer 60: 722–728.
Satoh, K., Narumi, K., Isemura, M., Sakai, T., Abe, T., Matsushima, K., Okuda, K. & Motomiya, M. (1992). Increased expression of the 67 kDa-laminin receptor gene in human small cell lung cancer. Biochem Biophys Res Commun 182: 746–752.
Shi, Y. E., Torri, J., Yieh, L., Sobel, M. E., Yamada, Y., Lippman, M. E., Dickson, R. B. & Thompson, E. W. (1993). Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins. Clin Exp Metastasis 11: 251–261.
Sobel, M. E. (1993). Differential expression of the 67-kDa laminin receptor in cancer. Semin Cancer Biol 4: 311–317.
Tapscott, S. J., Miller, A. D., Olson, J. M., Berger, M. S., Groudine, M. & Spence, A. M. (1994). Gene therapy of rat 9L gliosarcoma; tumours by transduction with selectable genes does not require drug selection. Proc Natl Acad Sci USA 91: 8185–8189.
Vacca, A., Ribatti, D., Roncali, L., Lospalluti, M., Seri, G., Carrel, S. & Dammacco, F. (1993). Melanocyte tumor progression is associated with changes in angiogenesis and expression of the 67-kilodalton laminin receptor. Cancer 72: 455–461.
Wang, K. S., Kuhn, R. J., Strauss, E. G., Ou, S. & Strauss, J. H. (1992). High-affinity laminin receptor is a receptor for Sindobis virus in mammalian cells. J Virol 66: 4992–5001.
Wewer, U. M., Taraboletti, G., Sobel, M. E., Albrechtsen, R. & Liotta, L. A. (1987). Role of laminin receptor in tumor cell migration. Cancer Res 47: 5691–5698.
Yang, G., Douville, P., Gee, S. & Carbonetto, S. (1992). Nonintegrin laminin receptors in the nervous system: evidence for lack of a relationship to p40. J Neurobiol 23: 491–506.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Satoh, K., Narumi, K., Abe, T. et al. Diminution of 37-kDa laminin binding protein expression reduces tumour formation of murine lung cancer cells. Br J Cancer 80, 1115–1122 (1999). https://doi.org/10.1038/sj.bjc.6690474
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690474
Keywords
This article is cited by
-
RETRACTED ARTICLE: 67-kDa laminin receptor induces FasL expression and FasL-mediated apoptosis through the activation of c-Myc and the subsequent activation of the FasL promoter in human cholangiocarcinoma cells
Journal of Cancer Research and Clinical Oncology (2011)
-
Proteomic analysis of human epithelial ovarian cancer xenografts in immunodeficient mice exposed to chronic psychological stress
Science China Life Sciences (2011)
-
Extraribosomal functions associated with the C terminus of the 37/67 kDa laminin receptor are required for maintaining cell viability
Cell Death & Disease (2010)
-
The Role of MAPK-ERK Pathway in 67-kDa Laminin Receptor-Induced FasL Expression in Human Cholangiocarcinoma Cells
Digestive Diseases and Sciences (2010)