Abstract
Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig5_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig6_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig7_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig8_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig9_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig10_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12013-021-00972-3/MediaObjects/12013_2021_972_Fig11_HTML.png)
Similar content being viewed by others
References
Miner, J. H., Patton, B. L., Lentz, S. I., Gilbert, D. J., Snider, W. D., Jenkins, N. A., Copeland, N. G., & Sanes, J. R. (1997). The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha3 isoform. Journal of Cell Biology, 137(3), 685–701.
Durbeej, M. (2010). Laminins. Cell and Tissue Research, 339(1), 259–68.
Cloutier, G., Sallenbach-Morrissette, A., & Beaulieu, J. F. (2019). Non-integrin laminin receptors in epithelia. Tissue and Cell, 56, 71–8.
Yamada, M., & Sekiguchi, K. (2015). Molecular basis of laminin-integrin interactions. Current Topics in Membranes, 76, 197–229.
Ishikawa, T., Wondimu, Z., Oikawa, Y., Gentilcore, G., Kiessling, R., Egyhazi Brage, S., Hansson, J., & Patarroyo, M. (2014). Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146). Matrix Biology, 38, 69–83.
Kato, R., Iwamuro, M., Shiraha, H., Horiguchi, S., Tanaka, E., Matsumoto, K., Ohyama, A., Sawahara, H., Nagahara, T., Uchida, D., Tsutsumi, K., & Okada, H. (2018). Dipeptide γ-secretase inhibitor treatment enhances the anti-tumor effects of cisplatin against gastric cancer by suppressing cancer stem cell properties. Oncology Letters, 16(4), 5426–32.
Kikkawa, Y., Sanzen, N., & Sekiguchi, K. (1998). Isolation and characterization of laminin-10/11 secreted by human lung carcinoma cells. laminin-10/11 mediates cell adhesion through integrin alpha3 beta1. Journal of Biological Chemistry, 273(25), 15854–9.
Ferletta, M., & Ekblom, P. (1999). Identification of laminin-10/11 as a strong cell adhesive complex for a normal and a malignant human epithelial cell line. Journal of Cell Science, 112(Pt 1), 1–10.
Pouliot, N., & Kusuma, N. (2013). Laminin-511: a multi-functional adhesion protein regulating cell migration, tumor invasion and metastasis. Cell Adhesion & Migration, 7(1), 142–149.
Miner, J. H., & Yurchenco, P. D. (2004). Laminin functions in tissue morphogenesis. Annual Review of Cell and Developmental Biology, 20, 255–84.
Kong, D. (2011). Cancer stem cells & epithelial-to-mesenchymal transition (EMT)-phenotypic cells: are they cousins or twins? Cancers, 3(1), 716–29.
Wang, S. S., Jiang, J., Liang, X. H., & Tang, Y. L. (2015). Links between cancer stem cells and epithelial-mesenchymal transition. OncoTargets and Therapy, 8, 2973–80.
Takatsuki, H., Komatsu, S., Sano, R., Takada, Y., & Tsuji, T. (2004). Adhesion of gastric carcinoma cells to peritoneum mediated by alpha3beta1 integrin (VLA-3). Cancer Research, 64(17), 6065–70.
Nishiuchi, R., Takagi, J., Hayashi, M., Ido, H., Yagi, Y., Sanzen, N., Tsuji, T., Yamada, M., & Sekiguchi, K. (2006). Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins. Matrix Biology, 25(3), 189–97.
Fujiwara, H., Kikkawa, Y., Sanzen, N., & Sekiguchi, K. (2001). Purification and characterization of human laminin-8. Laminin-8 stimulates cell adhesion and migration through alpha3beta1 and alpha6beta1 integrins. Journal of Biological Chemistry, 276(20), 17550–8.
Fujiwara, H., Gu, J., & Sekiguchi, K. (2004). Rac regulates integrin-mediated endothelial cell adhesion and migration on laminin-8. Experimental Cell Research, 292(1), 67–77.
Kawataki, T., Yamane, T., Naganuma, H., Rousselle, R., Anduren, I., Tryggvason, K., & Patarroyo, M. (2007). Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. Experimental Cell Research, 313(18), 3819–31.
Takkunen, M., Ainola, M., Vainionpaa, N., Grenman, R., Patarroyo, M., Garcia de Herreros, A., Konttinen, Y. T., & Virtanen, I. (2008). Epithelial-mesenchymal transition downregulates laminin alpha5 chain and upregulates laminin alpha4 chain in oral squamous carcinoma. Histochemistry and Cell Biology, 130(3), 509–25.
Oikawa, Y., Hansson, J., Sasaki, T., Rousselle, P., Domogatskaya, A., Rodin, S., Tryggvason, K., & Patarroyo, M. (2011). Melanoma cells produce multiple laminin isoforms and strongly migrate on α5-laminin(s) via several integrin receptors. Experimental Cell Research, 317(8), 1119–33.
Friedl, P., & Wolf, K. (2009). Proteolytic interstitial cell migration: a five-step process. Cancer and Metastasis Reviews, 28(1-2), 129–35.
Linder, S. (2007). The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends in Cell Biology, 17(3), 107–17.
Lee, M. S., Kim, S., Kim, B. G., Won, C., Nam, S. H., Kang, S., Kim, H. J., Kang, M., Ryu, J., Song, H. E., Lee, D., Ye, S. K., Jeon, N. L., Kim, T. Y., Cho, N. H., & Lee, J. W. (2014). Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation. Biochimica et Biophysica Acta, 1843(9), 2037–54.
Coopman, P. J., Do, M. T., Thompson, E. W., & Mueller, S. C. (1998). Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity. Clinical Cancer Research, 4(2), 507–15.
Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 119(6), 1420–8.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Iwamuro, M., Shiraha, H., Oyama, A. et al. Laminin-411 and -511 Modulate the Proliferation, Adhesion, and Morphology of Gastric Cancer Cells. Cell Biochem Biophys 79, 407–418 (2021). https://doi.org/10.1007/s12013-021-00972-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-021-00972-3