Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study

详细信息    查看全文

• 作者：Sandra YY Fok (1)
  Jeffrey S Rubin (2)
  Fiona Pixley (3)
  John Condeelis (3)
  Filip Braet (1)
  Lilian L Soon (1)
  
• 刊名：BMC Cancer
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：6
• 期：1
• 全文大小：2342KB
• 参考文献：1. Petty RD, Nicolson MC, Kerr KM, Collie-Duguid E, Murray GI: Gene expression profiling in non-small cell lung cancer: from molecular mechanisms to clinical application. / Clin Cancer Res 2004, 10: 3237鈥?248. CrossRef
  2. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I: Diversity of gene expression in adenocarcinoma of the lung. / Proc Natl Acad Sci USA 2001, 98: 13784鈥?3789. CrossRef
  3. Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M: Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. / Proc Natl Acad Sci USA 2001, 98: 13790鈥?3795. CrossRef
  4. Bombi JA, Martinez A, Ramirez J, Grau JJ, Nadal A, Fernandez PL, Palacin A, Cardesa A: Ultrastructural and molecular heterogeneity in non-small cell lung carcinomas: study of 110 cases and review of the literature. / Ultrastruct Pathol 2002, 26: 211鈥?18. CrossRef
  5. Felding-Habermann B: Integrin adhesion receptors in tumor metastasis. / Clin Exp Metastasis 2003, 20: 203鈥?13. CrossRef
  6. Friedl P, Wolf K: Tumour-cell invasion and migration: diversity and escape mechanisms. / Nat Rev Cancer 2003, 3: 362鈥?74. CrossRef
  7. Noel AGC, Bajou K, Devy L, Kebers F, Lewalle JM, Maquoj E, Munaut C, Remacle A, Foidart JM: Emerging roles for proteinases in cancer. / Invasion Metastasis 1997, 17: 221鈥?39.
  8. Soon LL, Yie TA, Shvarts A, Levine AJ, Su F, Tchou-Wong KM: Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation. / J Biol Chem 2003, 278: 11465鈥?1470. CrossRef
  9. Zicha D, Dunn G, Jones G: Analyzing chemotaxis using the Dunn direct-viewing chamber. / Methods Mol Biol 1997, 75: 449鈥?57.
  10. Kohn EC, Francis EA, Liotta LA, Schiffmann E: Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. / Int J Cancer 1990, 46: 287鈥?92. CrossRef
  11. Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK, Schiffmann E: Tumor cell autocrine motility factor. / Proc Natl Acad Sci USA 1996, 83: 3302鈥?306. CrossRef
  12. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A: Involvement of chemokine receptors in breast cancer metastasis. / Nature 2004, 410: 50鈥?6. CrossRef
  13. Bailly M, Condeelis JS, Segall JE: Chemoattractant-induced lamellipod extension. / Microsc Res Tec 1998, 43: 433鈥?43. CrossRef
  14. DesMarais V, Ichetovkin I, Condeelis J, Hitchcock-DeGregori SE: Spatial regulation of actin dynamics: a tropomyosin-free, actin-rich compartment at the leading edge. / J Cell Sci 2002, 115: 4649鈥?660. CrossRef
  15. Gene Expression Omnibus [http://www.ncbi.nlm.nih.gov/geo/]
  16. Burridge K, Fath K, Kelly T, Nuckolls G, Turner C: Focal adhesions: transmembrane junctions between the extracellular matrix and cytoskeleton. / Annu Rev Cell Biol 1988, 4: 487鈥?25. CrossRef
  17. Condeelis J, Segall J: Intravital Imaging of Cell Movement in Tumors. / Nat Rev Cancer 2003, 3: 921鈥?30. CrossRef
  18. Friedl P, Hegerfeldt Y, Tusch M: Collective cell migration in morphogenesis and cancer. / Int J Dev Biol 2004, 48: 441鈥?49. CrossRef
  19. Regen CM, Horwitz AF: Dynamics of beta1 integrin-mediated adhesive contacts in motile fibroblasts. / J Cell Biol 1992, 119: 1347鈥?359. CrossRef
  20. Lu J, Xiao Y, Baudhuin LM, Hong G, Xy Yan: Role of ether-linked lysophosphatidic acids in ovarian cancer cells. / J Lipid Res 2002, 43: 463鈥?75.
  21. Ghosh M, Song X, Mouneimne G, Sidani M, Lawrence DS, Condeelis JS: Cofilin Promotes Actin Polymerization and Defines the Direction of Cell Motility. / Science 2004, 304: 743鈥?46. CrossRef
  22. Mouneimme G, Soon L, DesMarais V, Sidani M, Song Xiaoyan, Yip Shu-Chin, Ghosh M, Eddy R, Backer JM, Condeelis J: Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation. / J Cell Biol 2004, 166: 1鈥?2.
  23. Bottomley MJ, Salim K, Panayotou G: Phospholipid-binding protein domains. / Biochim Biophys Acta 1998, 1436: 165鈥?83.
  24. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L: A brain serine/threonine protein kinase activated by Cdc42 and Rac1. / Nature 1994, 367: 40鈥?6. CrossRef
  25. Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG: A role for Rac in Tiam1-induced membrane ruffling and invasion. / Nature 1995, 375: 338鈥?40. CrossRef
  26. Nobes CD, Hall A: Rho GTPases control polarity, protrusion, and adhesion during cell movement. / J Cell Biol 1999, 144: 1235鈥?244. CrossRef
  27. Suetsugu S, Miki H, Takenawa T: Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins. / Cell Motil Cytoskeleton 2002, 51: 113鈥?22. CrossRef
  28. Elson EL, Felder SF, Jay PY, Kolodney MS, Pasternak C: Forces in cell locomotion. / Biochem Soc Symp 1999, 65: 299鈥?14.
  29. Bailly M, Condeelis J: Cell motility: insights from the backstage. / Nat Cell Biol 2002, 4: 292鈥?94. CrossRef
  30. Irazoqui JE, Gladfelter AS, Lew DJ: Scaffold-mediated symmetry breaking by Cdc42. / Nat Cell Biol 2003, 5: 1062鈥?070. CrossRef
  31. Pawson T, Scott JD: Signaling through scaffold, anchoring, and adaptor proteins. / Science 1997, 278: 2075鈥?080. CrossRef
  32. Rogge L, Bianchi E, Biffi M, Bono E, Chang SY, Alexander H, Santini C, Ferrari G, Sinigaglia L, Seiler M, Neeb M, Mous J, Sinigaglia F, Certa U: Transcript imaging of the development of human T helper cells using oligonucleotide arrays. / Nat Genet 2000, 25: 96鈥?01. CrossRef
  33. Tang P, Cheng TP, Agnello D, Wu CY, Hissong BD, Watford WT, Ahn HJ, Galon J, Moss J, Vaughan M, O'Shea JJ, Gadina M: Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity. / Proc Natl Acad Sci USA 2002, 99: 2625鈥?629. CrossRef
  34. Weidner N: New paradigm for vessel intravasation by tumor cells. / Am J Pathol 2002, 160: 1937鈥?939.
  35. Kitano J, Kimura K, Yamazaki Y, Soda T, Shigemoto R, Nakajima Y, Nakanishi S: Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. / J Neurosci 2002, 22: 1280鈥?289.
  36. Soon L, Mouneimne G, Segall J, Wyckoff J, Condeelis J: Description and characterization of a chamber for viewing and quantifying cancer cell chemotaxis. / Cell Motil Cytoskeleton 2005, 62 (1) : 27鈥?4. CrossRef
  37. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/151/prepub
  
• 作者单位：Sandra YY Fok (1)
  Jeffrey S Rubin (2)
  Fiona Pixley (3)
  John Condeelis (3)
  Filip Braet (1)
  Lilian L Soon (1)
  
  1. Electron Microscope Unit, Australian Key Centre for Microscopy and Microanalysis, University of Sydney, 2006, NSW, Sydney, Australia
  2. Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, 20892, Bethesda, MD, USA
  3. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, 10461, Bronx, NY, USA
  
• ISSN：1471-2407

文摘

Background Non-small cell lung cancer is the most common cause of early casualty from malignant disease in western countries. The heterogeneous nature of these cells has been identified by histochemical and microarray biomarker analyses. Unfortunately, the morphological, molecular and biological variation within cell lines used as models for invasion and metastasis are not well understood. In this study, we test the hypothesis that heterogeneous cancer cells exhibit variable motility responses such as chemokinesis and chemotaxis that can be characterized molecularly. Methods A subpopulation of H460 lung cancer cells called KINE that migrated under chemokinetic (no gradient) conditions was harvested from Boyden chambers and cultured. Time-lapsed microscopy, immunofluorescence microscopy and microarray analyses were then carried out comparing chemokinetic KINE cells with the unselected CON cell population. Results Time-lapsed microscopy and analysis showed that KINE cells moved faster but less directionally than the unselected control population (CON), confirming their chemokinetic character. Of note was that chemokinetic KINE cells also chemotaxed efficiently. KINE cells were less adhesive to substrate than CON cells and demonstrated loss of mature focal adhesions at the leading edge and the presence of non-focalized cortical actin. These characteristics are common in highly motile amoeboid cells that may favour faster motility speeds. KINE cells were also significantly more invasive compared to CON. Gene array studies and real-time PCR showed the downregulation of a gene called, ROM, in highly chemokinetic KINE compared to mainly chemotactic CON cells. ROM was also reduced in expression in a panel of lung cancer cell lines compared to normal lung cells. Conclusion This study shows that cancer cells that are efficient in both chemokinesis and chemotaxis demonstrate high invasion levels. These cells possess different morphological, cytoskeletal and adhesive properties from another population that are only efficient at chemotaxis, indicating a loss in polarity. Understanding the regulation of polarity in the context of cell motility is important in order to improve control and inhibition of invasion and metastasis.