Browse > Article

Cell Behavior of Human Papillomavirus-immortalized and Tumorigenic Human Oral Keratinocytes Does Not Depend on the Integrin Expression  

Park, Kyung-Hee (Department of Oral Biochemistry and Craniomaxillofacial Reconstructive Sciences, Dental Research Institute, and BK21 CLS, Seoul National University School of Dentistry)
Min, Byung-Moo (Department of Oral Biochemistry and Craniomaxillofacial Reconstructive Sciences, Dental Research Institute, and BK21 CLS, Seoul National University School of Dentistry)
Publication Information
International Journal of Oral Biology / v.32, no.3, 2007 , pp. 93-101 More about this Journal
Abstract
Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.
Keywords
Cell behavior; Integrin; Extracellular matrix proteins; Oral cancer cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Allen, M.V., Smith, G.J., Juliano, R., Maygarden, S.J., and Mohler, J. L. Downregulation of the ${\beta}4$ integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia. Hum. Pathol. 2:311-318, 1998
2 Bonkhoff, H., Stein, U., and Remberg, K. Differential expression of ${alpha}6$ and ${\alpha}2$ very late antigen integrin in the normal, hyperplastic and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands. Hum. Pathol. 24:243-248, 1993   DOI   ScienceOn
3 D'Ardenne, A. J., Richman, P. I., Orthonne, M. A., McAuly, A. E., and Jordan, S. Coordinate expression of ${\alpha}6$ integrin laminin receptor subunit and laminin in breast cancer. J. Pathol. 165:213-220, 1991   DOI
4 Hashimoto-Uoshima, M., Yan, Y.Z., Schneider, G., and Aukhil, I. The alternatively spliced domains EIIIB and EIIIA of human fibronectin affect cell adhesion and spreading. J. Cell Sci. 110:2271-2280, 1997
5 Juliano, R. L., and Haskill, S. Signal transduction from the extracellular matrix. J. Cell BioI. 120:577-585, 1993   DOI
6 Kim, J. P., Zhang, K., Chen, J. D., Wynn, K. C., Kramer, R. H., and Woodley, D. T. Mechanism of human keratinocyte migration on fibronectin : unique roles of RGD site and integrins. J. Cell. Physiol. 151:443-450, 1992   DOI
7 Oktay, M., Wary, K.K., Dans, M., Birge, R.B., and Giancotti, F.G. Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2- terminal kinase and progression through the G1 phase of the cell cycle. J. Cell BioI. 145:1461-1469, 1999   DOI
8 Park, N.H., Min, B.M., Li, S.L., Huang, M.Z., Cherrick, H.M., and Doniger, J. Immortalization of normal human oral keratinocytes with type 16 human papillomavirus. Carcinogenesis 12:1627-1631, 1991   DOI   ScienceOn
9 Serini, G., Trusolino, L., and Saggiorato, E. Changes in integrin and E-cadherin expression in neoplastic versus normal thyroid tissue. J. Natl. Cancer Inst. 88:442-449, 1996   DOI
10 Sonnenberg, A., Calafat, J., Janssen, H., Daams, H., van der Raaijhelmer, L.M., Falcioni, R., Kennel, S.J., Aplin, J.D., Baker, J., and Loizidou, M. Integrin ${\alpha}6{\beta}4$ complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion. J. Cell Biol. 113:907-917, 1991   DOI
11 Thomas, G.J., Jones, J., and Speight, P.M. Integrin and oral cancer. Oral Oncol. 33:381-388, 1997   DOI   ScienceOn
12 Weinel, R., Rosendahl, A., Pinshmidt, E., Kisker, O., Simon, B., and Santoso, S. The ${\alpha}6$ integrin receptor in pancreatic carcinoma. Gastroenterology 108:523-532, 1995   DOI   ScienceOn
13 Varner, J.A., and Cheresh, D.A. Integrins and cancer. Curr. Opin. Cell BioI. 8:724-730, 1996   DOI   ScienceOn
14 Williams, M.J., Hughes, P.E., O'Toole, T.E., and Ginsberg, M.H. The inner world cell adhesions: integrin cytoplasmic domains. Trands Cell BioI. 4:109-112, 1994   DOI   ScienceOn
15 Witkowski, C.M., Bowden, G.T., Nagle, R.B., and Cress, A.E. Altered surface expression and increased turnover of the ${\alpha}6{\beta}4$ integrin in an undifferentiated carcinoma. Carcinogenesis 21:325-330, 2000   DOI   ScienceOn
16 Woodley, D.T., Bachmann, P., and O'Keefe, E.J. Laminin inhibits human keratinocytes migration. J. Cell. Physiol. 136:140-146,1988   DOI
17 Agrez, M.V, Bates, R.C., Mitchell, D., Wilson, N., Ferguson, N., and Anseline, P. Muliplicity of fibronectin-binding ${\alpha}V$ integrin receptors in colorectal cancer. Br. J. Cancer 73:887-892, 1996   DOI   ScienceOn
18 Albelda, S.M., and Buck, C.A. Integrins and other cell adhesion molecules. FASEB J. 4:2868-2880, 1990   DOI
19 Quaranta, V. Epitheilal integrins. Cell Differ. Dev. 32:361-365, 1990   DOI   ScienceOn
20 Sheppard. D., Rozzo. C., Starr, L., Quaranta, V., Erle, D.J., and Pytela, R. Complete amino sequence of a novel integrin ${\beta}$ subunit $({\beta}6)$ identified in epithelial cells using a polymerase chain reaction. J. BioI. Chem. 265:11502-11507, 1990
21 Sethi, T., Rintoul, R.C., Moore, S., MacKinnon, A.C., Salter, D., Choo, C., Chivers, E.R., Dransfield, I., Donnelly, S.C., Strieter, R., and Haslett, C. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a machanism for small cell lung cancer growth and drug resistance in vivo. Nat. Med. 5:662-668, 1999   DOI   ScienceOn
22 Carter, W.G, Kaur. P., Gil, S.G, Gahr, P.J., and Wayner, E.A. Distinct functions for integrin ${\alpha}3{\beta}1$ in focal adhesions and ${\alpha}6{\beta}4$/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes. J. Cell BioI. 111:3141-3154, 1990   DOI
23 Oh, J.E., Kook, J.K., and Min, B.M. ${\beta}ig$-h3 induces keratinocyte differentiation via modulation of involucrin and trans-glutaminase expression through the integrin ${\alpha}3{\beta}1$ and the phosphatidylinositol 3-kinase/Akt signaling pathway. J. BioI. Chem. 280:21629-21637, 2005   DOI   ScienceOn
24 Liebert, M., and Seigne, J. Characteristic of invasive bladder cancers: historical and molecular markers. Semin. Urol. Oncol. 14:62-72, 1996
25 O'Toole, E.A., Marinkobich, M.P., Hoeffler, W.K., Furthmayr, H., and Woodley, D.T. Laminin-5 inhibits human keratinocyte migration. Exp. Cell Res. 233:330-339, 1997   DOI   ScienceOn
26 Hynes, R.O. Integrin: versatility, modulation, and signaling in cell adhesion. Cell 69:11-25, 1992   DOI   ScienceOn
27 Natali, P.G., Nicotra, M.R., Botti, C., Mottolese, M., Bigotti, A., and Segatto, O. Changes in expression of ${\alpha}6{\beta}4$ integrin heterodimer in primary and metastatic breast cancer. Br. J. Cancer 66:318-322, 1992   DOI   ScienceOn
28 Pignatelli, M., Hanby, A.M., and Stamp, G.W. Low expression of ${beta}1,\;{\alpha}2\;and\;{\alpha}3$ subunits of VLA integrins in malignant mammary tumors. J. PathoI. 165:25-32, 1991   DOI
29 Hanby, A.M., Gillett, C.E., Pignatelli, M., and Stamp, G.W. ${\beta}1$ and ${\beta}4$ integrin expression in methacarn and formalin-fixed material from in situ ductal carcinoma of the breast. J. Pathol. 171:257-262, 1993   DOI   ScienceOn
30 Cheresh, D.A. Structral and biologic properties of integrin-mediated cell adhesion. Clin. Lab. Med. 12:217-236, 1992
31 Koretz, K., Schlag, P., Boumsell, L., and Moller, P. Expression of VLA- ${\alpha}2$, VLA- ${\alpha}6$, and VLA-{\beta}1$ chains in normal mucosa and adenomas of the colon, and in colocarcinoma and theirliver metastasis. Am. J. PathoI. 148:741-750, 1991
32 Min, B.M., Woo, K.M., Beak, J.H., Lee, G., and Park, N.H. Malignant transformation of HPV-immortalized human oral keratinocytes by chemical carcinogens. Int. J. Oncol. 7:249-256, 1995
33 Breuss, J.M., Gallo, J., De Lisser, H.M., Klimanskaya, I.U., Folkesson, H.G., and Pittet, J.F. Expression of the ${\beta}6$ integrin in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J. Cell Sci. 108:2241-2251, 1995
34 Gui, G.P., Wells, C.A, Browne, P.D., Yeomans, P., Jordan, S., Puddetoot, J.R., Vinson, G.P., and Carpenter, R. Integrin expression in primary breast cancer and its relation to axillary nodal status. Surgery 117:102-108, 1995   DOI   ScienceOn
35 Hughes, P.E., and Pfaff, M. Integrin affinity modulation. Trands Cell BioI. 8:359-364, 1998   DOI   ScienceOn
36 Kim, J. P., Chen, J. D., Wilke, M. S., Schall, T. J., and Woodley, D. T. Human keratinocyte migration on type IV collagen. Roles of heparin-binding site and ${\alpha}2{\beta}1$ integrin. Lab. Invest. 71:401-408, 1994
37 Miyazaki, K., Kikkawa, Y., Nakamura, A., Yasumitsu, H., and Umeda, M. A large cell-adhesive scatter factor secreted by human gastric carcinoma cells. Proc. Natl. Acad. Sci. USA 90:11767-11771, 1993
38 Lukashev, M., and Werb, Z. ECM signaling: orchestrating cell behavior and misbehavior. Trands Cell BioI. 8:437-441, 1998   DOI   ScienceOn
39 Symington, B.E., Takada, Y., and Carter, W.G. Interaction of integrin ${\alpha}3{\beta}1\;and\;{\alpha}2{\beta}1$: potential role in keratinocyte intercellular adhesion. J. Cell BioI. 120:523-535, 1993   DOI
40 Friederichs, K., Ruiz, P., Folker, F., Gille, I., Terpe, H.J., and Imhof, B.A. High expression level of ${\alpha}6$ integrin in human breast carcinoma is correlated with reduced survival. Cancer Res. 55:901-906, 1995
41 Downer, C.S., Watt, F.M., and Speight, P.M. Loss of ${\alpha}6$ and ${\beta}4$ integrin subunits coincides with loss of basement membrane components in oral squamous cell carcinomas. J. Pathol. 171:183-190, 1993   DOI   ScienceOn
42 Zutter, M., Mazoujian, M., and Santoro, S.A. Decreased expression of integrin adhesive protein receptors in adenocarcinoma of breast. Am. J. Pathol. 137:863-870, 1990
43 Hodivala, K.J., Pei, X.F., Liu, Q.Y., Jones, P.H., Rytina, E.R., Gilbert, C., Singer, A., and Watt, F.M. Integrin expression and function in HPV 16-immortalized human keratinocytes in the presence or absence of v-Ha-ras. Comparison with cervical intraepithelial neoplasia. Oncogene 9:943-948, 1994
44 Rodeck, U., Jost, M., Kari, C., Shih, D. T., Lavker, R. M., Ewert, D. L., and Jensen, P. J. EGF-R dependent regulation ofkeratinocyte survival. J. Cell Sci. 110:113-121, 1997
45 Adams, J.C., and Watt, F.M. Regulation of development and differentiation by the extracellular matrix. Development 117:1183-1193, 1993
46 Watt, F.M., and Hertle, M.D. Keratinocyte integrins. In Leigh, I.M., Lane,E.B., and Watt, F.M. (eds), The Keratinocyte Handbook. pp 153-164, Cambridge University Press, Cambridge, 1994
47 Pignatelli, M., Smith, M.E., and Bodmer, W.F. Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br. J. Cancer 61:636-638, 1990   DOI   ScienceOn
48 Hall, P.A., Coates, P., Lemoine, N.and R., and Horthons, M.A. Characterization of integrin chains in normal and neoplastic human pancreas. J. Pathol. 108:523-532, 1991
49 Maragou P., Bazopoulou-Kyrkanidou E., Panotopoulou E., Kakarantza-Angelopoulou E., Sklavounou-Andrikopoulou A, and Kotaridis S. Alteration of integrin expression in oral squamous cell carcinomas. Oral Dis. 5:20-26, 1999   DOI   ScienceOn
50 Plantefaber, L. C., and Hynes, R. O. Changes in integrin receptors on oncogenic ally trasformed cells. Cell 56:281-290, 1989   DOI   ScienceOn
51 Giancotti, F.G, and Ruoslhti, E. Integrin signaling. Science 285:1028-1032, 1999   DOI   ScienceOn
52 Jones, J., Watt, F.M., and Speight, P.M. Changes in the expression of ${\alpha}v$ integrins in oral squamous cell carcinomas. J. Oral Pathol. Med. 26:63-68, 1997   DOI   ScienceOn
53 Savoia, P., Trusolino, L., Pepino, E., Cremona, O., and Marchisio, P.C. Expression and topography of integrins and basement membrane proteins in epidermal carcinomas: basal but not squamous cell carcinoma display loss of ${\alpha}6{\beta}4$ and BM-600/nicein. J. Invest. Dermatol. 101:352-358, 1993   DOI   ScienceOn
54 Hynes, R.O. Cell adhesion: old and new questions. Trends Cell BioI. 9:M33-M37, 1999   DOI   ScienceOn
55 Koukolis, G.K., Virtanen, I., Korhonen, M., Laitinen, L., Quaranta, V., and Gould, V.E. Immunohistochemical localization of integrins in the normal, hyperplastic, and. neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules. Am. J. Pathol. 139:787-799, 1991
56 Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W.G., and Quaranta, V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277:225-228, 1997   DOI   ScienceOn
57 Shofield, O., Kist, D., Lucas, A., Wayner, E., Carter, W., and Zachary, C. Abnormal expression of epiligrin and ${\alpha}6{\beta}4$ integrin in basal cell carcinoma. Dermatol. Surg. 24:555-559, 1998   DOI
58 Cress, A.E., Rabinovitz, I., Zhu, W., and Nagle, R.B. The ${\alpha}6{\beta}1$ and ${\alpha}6{\beta}4$ integrin in human prostate cancer progression. Cancer Metastasis Rev. 14:219-228, 1995   DOI
59 Lee, G., Kim Y.B., Kim, J.H., Kim, M.S., Shin, K.H., Won, Y.S., Lee, J.I., Choung, P.H., Hyun, B.H., and Min, B.M. Characterization of novel cell lines established from three human oral squamous cell carcinomas. Int. J. Oncol. 20:1151-1159, 2002
60 Liebert, M., Wedemeyer, G., and Stein, J.A. The monoclonal antibody BQ 16 identifies the ${\alpha}6{\beta}4$ integrin on bladder cancer. Hybridoma 12:67-80, 1993   DOI
61 Sashiyama, H., Shino, Y., Sakao, S., Shimada, H., Kobayashi, S., Ochiai, T., and Shirasawa, H. Alteration of integrin expression relates to malignant progression of human papillomavirus-immortalized esophageal keratinocytes. Cancer Lettters 177:21-28, 2002   DOI   ScienceOn
62 Mainiero, M., Murgia, C., Wary, K.K., Curatola, A.M., Pepe, A., Blumemberg, M., Westwick, J.K., Der, C.J., and Giancotti, F.G. The coupling of ${\alpha}6{\beta}4$ integrin to Ras-MAP kinase pathways mediated by She controls keratinocyte proliferation. EMBO J. 16:2365-2375, 1997   DOI   ScienceOn
63 Rabinovitz, I., and Mercurio, A.M. The integrin ${\alpha}6{\beta}4$ and the biology of carcinoma. Biochem. Cell BioI. 74:811-821, 1996   DOI   ScienceOn