Expression of laminin γ2 chain monomer enhances invasive growth of human carcinoma cells in vivo
Yoshiaki Tsubota
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorTakashi Ogawa
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorJun Oyanagi
Department of Genome System Science, Graduate School of Nanobioscience, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorYoji Nagashima
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan
Search for more papers by this authorCorresponding Author
Kaoru Miyazaki
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Department of Genome System Science, Graduate School of Nanobioscience, Yokohama City University, Totsuka-ku, Yokohama, Japan
Tel.: +81-45-820-1905, Fax: +81-45-820-1901 (or +81-466-87-3391)
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University; 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, JapanSearch for more papers by this authorYoshiaki Tsubota
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorTakashi Ogawa
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorJun Oyanagi
Department of Genome System Science, Graduate School of Nanobioscience, Yokohama City University, Totsuka-ku, Yokohama, Japan
Search for more papers by this authorYoji Nagashima
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan
Search for more papers by this authorCorresponding Author
Kaoru Miyazaki
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Totsuka-ku, Yokohama, Japan
Department of Genome System Science, Graduate School of Nanobioscience, Yokohama City University, Totsuka-ku, Yokohama, Japan
Tel.: +81-45-820-1905, Fax: +81-45-820-1901 (or +81-466-87-3391)
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University; 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, JapanSearch for more papers by this authorAbstract
Laminin γ2 chain is a subunit of the heterotrimeric basement membrane protein laminin-332 (α3β3γ2). The γ2 chain is highly expressed by human cancers at the invasion fronts and this expression correlates with poor prognosis of the cancers. Our previous study showed that the γ2 chain is expressed as a monomer form in invading carcinoma cells. However, the role of the γ2 protein in tumor invasion remains unknown. Here, we demonstrate that the monomeric γ2 chain promotes invasive growth of human cancer cells in vivo. First, we analyzed regulatory factors for the γ2 chain expression using 2 gastric carcinoma cell lines. It was found that tumor necrosis factor-α, by itself or in a combination with transforming growth factor-β1, strongly induced the secretion of the monomeric γ2 chain. In addition, epidermal growth factor families appeared to function as the γ2 chain inducers in human cancers. Next, we established T-24 bladder carcinoma cell lines expressing the full-length or the short arm of the laminin γ2 chain. When these cell lines were i.p. injected into nude mice, they produced larger tumors in the abdominal cavity and showed much stronger invasive growth onto the diaphragms than the control cell line. The γ2-expressing T-24 cells often produced ascites fluid, but scarcely the control cells. In culture, the γ2-expressing cells migrated through Matrigel more efficiently than the control cells. These findings imply that the γ2 monomer is induced in human cancers by inflammatory and stromal cytokines and promotes their invasive growth in vivo.
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References
- 1
Colognato H,
Yurchenco PD.
Form and function: the laminin family of heterotrimers.
Dev Dyn
2000;
218:
213–34.
10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R CAS PubMed Web of Science® Google Scholar
- 2 Baker SE, Hopkinson SB, Fitchmun M, Andreason GL, Frasier F, Plopper G, Quaranta V, Jones JC. Laminin-5 and hemidesmosomes: role of the α3 chain subunit in hemidesmosome stability and assembly. J Cell Sci 1996; 109: 2509–20.
- 3 Rousselle P, Keene DR, Ruggiero F, Champliaud MF, Rest M, Burgeson RE. Laminin-5 binds the NC-1 domain of type VII collagen. J Cell Biol 1997; 138: 719–28.
- 4 Miyazaki K, Kikkawa Y, Nakamura A, Yasumitsu H, Umeda M. A large cell-adhesive scatter factor secreted by human gastric carcinoma cells. Proc Natl Acad Sci USA 1993; 90: 11767–71.
- 5 Mizushima H, Miyagi Y, Kikkawa Y, Yamanaka N, Yasumitsu H, Misugi K, Miyazaki K. Differential expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promoter and growth factors. J Biochem 1996; 120: 1196–202.
- 6 Kikkawa Y, Umeda M, Miyazaki K. Marked stimulation of cell adhesion and motility by ladsin, a laminin-like scatter factor. J Biochem 1994; 116: 862–9.
- 7
Fukushima Y,
Ohnishi T,
Arita N,
Hayakawa T,
Sekiguchi K.
Integrin α3β1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells.
Int J Cancer
1998;
76:
63–72.
10.1002/(SICI)1097-0215(19980330)76:1<63::AID-IJC11>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- 8 Miyazaki K. Laminin-5 (laminin-332): unique biological activity and role in tumor growth and invasion. Cancer Sci 2006; 97: 91–8.
- 9 Marinkovich MP. Tumour microenvironment: laminin 332 in squamous-cell carcinoma. Nat Rev Cancer 2007; 7: 370–80.
- 10 Katayama M, Sekiguchi K. Laminin-5 in epithelial tumour invasion. J Mol Histol 2004; 35: 77–86.
- 11 Pyke C, Rømer J, Kallunki P, Lund LR, Ralfkiaer E, Danø K, Tryggvason K. The γ 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers. Am J Pathol 1994; 145: 782–91.
- 12
Soini Y,
Määttä M,
Salo S,
Tryggvason K,
Autio-Harmainen H.
Expression of the laminin γ 2 chain in pancreatic adenocarcinoma.
J Pathol
1996;
180:
290–4.
10.1002/(SICI)1096-9896(199611)180:3<290::AID-PATH661>3.0.CO;2-6 PubMed Web of Science® Google Scholar
- 13 Takahashi S, Hasebe T, Oda T, Sasaki S, Kinoshita T, Konishi M, Ochiai T, Ochiai A. Cytoplasmic expression of laminin γ2 chain correlates with postoperative hepatic metastasis and poor prognosis in patients with pancreatic ductal adenocarcinoma. Cancer 2002; 94: 1894–901.
- 14 Koshikawa N, Moriyama K, Takamura H, Mizushima H, Nagashima Y, Yanoma S, Miyazaki K. Overexpression of laminin γ2 chain monomer in invading gastric carcinoma cells. Cancer Res 1999; 59: 5596–601.
- 15
Ono Y,
Nakanishi Y,
Ino Y,
Niki T,
Yamada T,
Yoshimura K,
Saikawa M,
Nakajima T,
Hirohashi S.
Clinicopathologic significance of laminin-5 γ2 chain expression in squamous cell carcinoma of the tongue: immunohistochemical analysis of 67 lesions.
Cancer
1999;
85:
2315–21.
10.1002/(SICI)1097-0142(19990601)85:11<2315::AID-CNCR3>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar
- 16
Sordat I,
Bosman FT,
Dorta G,
Rousselle P,
Aberdam D,
Blum AL,
Sordat B.
Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia.
J Pathol
1998;
185:
44–52.
10.1002/(SICI)1096-9896(199805)185:1<44::AID-PATH46>3.0.CO;2-A CAS PubMed Web of Science® Google Scholar
- 17 Hlubek F, Jung A, Kotzor N, Kirchner T, Brabletz T. Expression of the invasion factor laminin γ2 in colorectal carcinomas is regulated by β-catenin. Cancer Res 2001; 61: 8089–93.
- 18 Kagesato Y, Mizushima H, Koshikawa N, Kitamura H, Hayashi H, Ogawa N, Tsukuda M, Miyazaki K. Sole expression of laminin γ 2 chain in invading tumor cells and its association with stromal fibrosis in lung adenocarcinomas. Jpn J Cancer Res 2001; 92: 184–92.
- 19 Skyldberg B, Salo S, Eriksson E, Aspenblad U, Moberger B, Tryggvason K, Auer G. Laminin-5 as a marker of invasiveness in cervical lesions. J Natl Cancer Inst 1999; 91: 1882–7.
- 20 Yamamoto H, Itoh F, Iku S, Hosokawa M, Imai K. Expression of the γ(2) chain of laminin-5 at the invasive front is associated with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Clin Cancer Res 2001; 7: 896–900.
- 21 Gasparoni A, Della Casa M, Milillo L, Lorenzini G, Rubini C, Urso R, Lo Muzio L. Prognostic value of differential expression of Laminin-5 γ2 in oral squamous cell carcinomas: correlation with survival. Oncol Rep 2007; 18: 793–800.
- 22 Driemel O, Dahse R, Hakim SG, Tsioutsias T, Pistner H, Reichert TE, Kosmehl H. Laminin-5 immunohistochemistry: a new tool for identifying dysplastic cells in oral brush biopsies. Cytopathology 2007; 18: 348–55.
- 23 Hirosaki T, Mizushima H, Tsubota Y, Moriyama K, Miyazaki K. Structural requirement of carboxyl-terminal globular domains of laminin α3 chain for promotion of rapid cell adhesion and migration by laminin-5. J Biol Chem 2000; 275: 22495–502.
- 24 Katayama M, Funakoshi A, Sumii T, Sanzen N, Sekiguchi K. Laminin γ2-chain fragment circulating level increases in patients with metastatic pancreatic ductal cell adenocarcinomas. Cancer Lett 2005; 225: 167–76.
- 25 Guess CM, Lafleur BJ, Weidow BL, Quaranta V. A decreased ratio of laminin-332 β3 to γ2 subunit mRNA is associated with poor prognosis in colon cancer. Cancer Epidemiol Biomarkers Prev 2009; 18: 1584–90.
- 26 Ogawa T, Tsubota Y, Maeda M, Kariya Y, Miyazaki K. Regulation of biological activity of laminin-5 by proteolytic processing of γ2 chain. J Cell Biochem 2004; 92: 701–14.
- 27 Miyazaki K, Hattori Y, Umenishi F, Yasumitsu H, Umeda M. Purification and characterization of extracellular matrix-degrading metalloproteinase, matrin (pump-1), secreted from human rectal carcinoma cell line. Cancer Res 1990; 50: 7758–64.
- 28 Olsen J, Lefebvre O, Fritsch C, Troelsen JT, Orian-Rousseau V, Kedinger M, Simon-Assmann P. Involvement of activator protein 1 complexes in the epithelium-specific activation of the laminin γ2-chain gene promoter by hepatocyte growth factor (scatter factor). Biochem J 2000; 347: 407–17.
- 29 Korang K, Christiano AM, Uitto J, Mauviel A. Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, α 3, β 3, and γ 2, of human laminin 5 in epidermal keratinocytes. FEBS Lett 1995; 368: 556–8.
- 30 Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 2009; 457: 102–6.
- 31 Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860–7.
- 32 Franz M, Richter P, Geyer C, Hansen T, Acuña LD, Hyckel P, Böhmer FD, Kosmehl H, Berndt A. Mesenchymal cells contribute to the synthesis and deposition of the laminin-5 γ2 chain in the invasive front of oral squamous cell carcinoma. J Mol Histol 2007; 38: 183–90.
- 33 Prime SS, Davies M, Pring M, Paterson IC. The role of TGF-β in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II). Crit Rev Oral Biol Med 2004; 15: 337–47.
- 34 Peinado H, Quintanilla M, Cano A. Transforming growth factor β-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem 2003; 278: 21113–23.
- 35 Kinzler K, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87: 159–70.
- 36 Koshikawa N, Giannelli G, Cirulli V, Miyazaki K, Quaranta V. Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. J Cell Biol 2000; 148: 615–24.
- 37 Schenk S, Hintermann E, Bilban M, Koshikawa N, Hojilla C, Khokha R, Quaranta V. Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution. J Cell Biol 2003; 161: 197–209.
- 38 Decline F, Rousselle P. Keratinocyte migration requires α2β1 integrin-mediated interaction with the laminin 5 γ2 chain. J Cell Sci 2001; 114: 811–23.
- 39 Ogawa T, Tsubota Y, Hashimoto J, Kariya Y, Miyazaki K. The short arm of laminin γ2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin β4 chain. Mol Biol Cell 2007; 18: 1621–33.
- 40 Yuen H, Ziober AF, Gopal P, Nasrallah I, Falls EM, Meneguzzi G, Ang HQ, Ziober BL. Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion. Exp Cell Res 2005; 309: 198–210.
- 41 Salo S, Boutaud A, Hansen AJ, He L, Sun Y, Morales S, Venturini A, Martin P, Nokelainen P, Betsholtz C, Mathiasen IS, Tryggvason K. Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit tumor growth and metastasis in vivo. Int J Cancer 2009; 125: 1814–25.
- 42 Mizushima H, Koshikawa N, Moriyama K, Takamura H, Nagashima Y, Hirahara F, Miyazaki K. Wide distribution of laminin-5 γ2 chain in basement membranes of various human tissues. Hormone Res 1998; 50 ( Suppl 2): 7–14.
- 43 Hindermann W, Berndt A, Haas KM, Wunderlich H, Katenkamp D, Kosmehl H. Immunohistochemical demonstration of the γ2 chain of laminin-5 in urinary bladder urothelial carcinoma—impact for diagnosis and prognosis. Cancer Detect Prev 2003; 27: 109–14.