Skip to main content
PMC home page
Cancer Science logoLink to Cancer Science
. 2005 Aug 19;95(2):142–148. doi: 10.1111/j.1349-7006.2004.tb03195.x

Increased expression of integrin α3β1 in highly brain metastatic subclone of a human non‐small cell lung cancer cell line

Tatsuya Yoshimasu 1,✉, Teruhisa Sakurai 1,✉, Shoji Oura 1,✉, Issei Hirai 1,✉, Hirokazu Tanino 1,✉, Yozo Kokawa 1,✉, Yasuaki Naito 1,✉, Yoshitaka Okamura 1,✉, Ichiro Ota 2,✉, Naoyuki Tani 2,✉, Nariaki Matsuura 2,✉
PMCID: PMC11158200  PMID: 14965364

Abstract

To clarify the roles of integrin and extracellular matrix (ECM) in the process of non‐small cell lung cancer (NSCLC) brain metastasis, we established an in vivo model of brain metastasis of human NSCLC cell line EBC‐1/original in athymic mice, and established highly brain metastatic subclone EBC‐1/brain and highly bone metastatic subclone EBC‐1/bone. Integrin expression of these subclones was evaluated by flow cytometry. In vitro cell attachment, migration and proliferation assays with ECMs were performed using these subclones. Expression of integrin α3 subunit was higher in EBC‐1/brain than in both EBC‐1/original and EBC‐1/bone. In vitro cell attachment, migration, and proliferation assays revealed that EBC‐1/brain had higher affinity and higher reactivity to laminin than EBC‐1/original and EBC‐1/bone. Blocking of integrin α3β1 significantly (P<0.05) decreased brain metastasis by EBC‐1/brain. Interaction of integrin α3β1 and laminin plays important roles in the process of brain metastasis of non‐small cell lung cancer.

References

  • 1. Kishi K, Nomura K, Miki Y, Shibui S, Takakura K. Metastatic brain tumor. A clinical and pathologic analysis of 101 cases with biopsy. Arch Pathol Lab Med 1982; 106: 133–5. [PubMed] [Google Scholar]
  • 2. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69: 11–25. [DOI] [PubMed] [Google Scholar]
  • 3. Chan BM, Matsuura N, Takada Y, Zetter BR, Hemler ME. In vitro and in vivo consequences of VLA‐2 expression on rhabdomyosarcoma cells. Science 1991; 251: 1600–2. [DOI] [PubMed] [Google Scholar]
  • 4. Matsuura N, Puzon‐McLaughlin W, Me A, Morikawa Y, Kakudo K, Takada Y. Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells. Am J Pathol 1996; 148: 55–61. [PMC free article] [PubMed] [Google Scholar]
  • 5. Rutka JT, Apodaca G, Stern R, Rosenblum M. The extracellular matrix of the central and peripheral nervous systems: structure and function. J Neurosurg 1988; 69: 155–70. [DOI] [PubMed] [Google Scholar]
  • 6. Knott JC, Mahesparan R, Garcia‐Cabrera I, Bolge Tysnes B, Edvardsen K, Ness GO, Mork S, Lund‐Johansen M, Bjerkvig R. Stimulation of extracellular matrix components in the normal brain by invading glioma cells. Int J Cancer 1988; 75: 864–72. [DOI] [PubMed] [Google Scholar]
  • 7. Fidler IJ, Schackert G, Zhang RD, Radinsky R, Fujimaki T. The biology of melanoma brain metastasis. Cancer Metastasis Rev 1999; 18: 387–400. [DOI] [PubMed] [Google Scholar]
  • 8. Nicolson GL, Brunson KW, Fidler IJ. Specificity of arrest, survival, and growth of selected metastatic variant cell lines. Cancer Res 1978; 38: 4105–11. [PubMed] [Google Scholar]
  • 9. Albelda SM, Mette SA, Elder DE, Stewart R, Damjanovich L, Herlyn M, Buck CA. Integrin distribution in malignant melanoma: association of the 3 subunit with tumour progression. Cancer Res 1990; 50: 6757–64. [PubMed] [Google Scholar]
  • 10. Rooprai HK, Vanmeter T, Panou C, Schnull S, Trillo‐Pazos G, Davies D, Pilkington GJ. The role of integrin receptors in aspects of glioma invasion in vitro. Int J Dev Neurosci 1999; 17: 613–23. [DOI] [PubMed] [Google Scholar]
  • 11. Paulus W, Baur I, Schuppan D, Roggendorf W. Characterization of integrin receptors in normal and neoplastic human brain. Am J Pathol 1993; 143: 154–63. [PMC free article] [PubMed] [Google Scholar]
  • 12. Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ. In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia (New York) 1999; 1: 50–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Matsui T, Ota T, Ueda Y, Tanino M, Odashima S. Isolation of a highly metastatic cell line to lymph node in human oral squamous cell carcinoma by orthotopic implantation in nude mice. Oral Oncol 1998; 34: 253–6. [PubMed] [Google Scholar]
  • 14. Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ, Fidler IJ. Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 1996; 2: 1627–36. [PubMed] [Google Scholar]
  • 15. Vezeridis MP, Tzanakakis GN, Meitner PA, Doremus CM, Tibbetts LM, Calabresi P. In vivo selection of a highly metastatic cell line from a human pancreatic carcinoma in the nude mouse. Cancer 1992; 69: 2060–3. [DOI] [PubMed] [Google Scholar]
  • 16. Bartolazzi A, Cerboni C, Nicotra MR, Mottolese M, Bigotti A, Natali PG. Transformation and tumor progression are frequently associated with expres sion of the alpha 3/beta 1 heterodimer in solid tumors. Int J Cancer 1994; 58: 488–91. [DOI] [PubMed] [Google Scholar]
  • 17. Morini M, Mottolese M, Ferrari N, Ghiorzo F, Buglioni S, Mortarini R, Noonan DM, Natali PG, Albini A. The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP‐9) activity. Int J Cancer 2000; 87: 336–42. [PubMed] [Google Scholar]
  • 18. Ura H, Denno R, Hirata K, Yamaguchi K, Yasoshima T. Separate functions of alpha 2 beta 1 and alpha 3 beta 1 integrins in the metastatic process of human gastric carcinoma. Surg Today 1998; 28: 1001–6. [DOI] [PubMed] [Google Scholar]
  • 19. Prokopishyn NL, Puzon‐McLaughlin W, Takada Y, Laferte S. Integrin alpha 3 beta 1 expressed by human colon cancer cells is a major carrier of oncodevelopmental carbohydrate epitopes. J Cell Biochem 1999; 72: 189–209. [PubMed] [Google Scholar]
  • 20. Yoshinaga IG, Vink J, Dekker SK, Mihm MC Jr, Byers HR. Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration. Melanoma Res 1993; 3: 435–41. [DOI] [PubMed] [Google Scholar]
  • 21. Melchiori A, Mortarini R, Carlone S, Marchisio PC, Anichini A, Noonan DM, Albini A. The alpha 3 beta 1 integrin is involved in melanoma cell migration and invasion. Exp Cell Res 1995; 219: 233–42. [DOI] [PubMed] [Google Scholar]
  • 22. Goldbrunner RH, Haugland HK, Klein CE, Kerkau S, Roosen K, Tonn JC. ECM dependent and integrin mediated tumor cell migration of human glioma and melanoma cell lines under serum‐free conditions. Anticancer Res 1996; 16: 3679–87. [PubMed] [Google Scholar]
  • 23. Chintala SK, Sawaya R, Gokaslan ZL, Rao JS. Modulation of matrix metalloprotease‐2 and invasion in human glioma cells by alpha 3 beta 1 integrin. Cancer Lett 1996; 103: 201–8. [DOI] [PubMed] [Google Scholar]
  • 24. Tysnes BB, Larsen LF, Ness GO, Mahesparan R, Edvardsen K, Garcia‐Cabrera I, Bjerkvig R. Stimulation of glioma‐cell migration by laminin and inhibition by anti‐alpha 3 and anti‐beta 1 integrin antibodies. Int J Cancer 1996; 67: 777–84. [DOI] [PubMed] [Google Scholar]
  • 25. Frade JM, Martinez‐Morales JR, Rodriguez‐Tebar A. Laminin‐1 selectively stimulates neuron generation from cultured retinal neuroepithelial cells. Exp Cell Res 1996; 222: 140–9. [DOI] [PubMed] [Google Scholar]
  • 26. Cohen J, Burne JF, McKinlay C, Winter J. The role of laminin and the laminin/fibronectin receptor complex in the outgrowth of retinal ganglion cell axons. Dev Biol (Orlando) 1987; 122: 407–18. [DOI] [PubMed] [Google Scholar]
  • 27. Clark P, Britland S, Connolly P. Growth cone guidance and neuron morphology on micropatterned laminin surfaces. J Cell Sci 1993; 105: 203–12. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Science are provided here courtesy of Wiley

RESOURCES