Abstract
The Dunning rat prostatic carcinoma is a model system where cell motility closely correlates with the metastatic phenotype. We have identified a novel gene, upregulated in the highly motile and metastatic Dunning cancer cell lines, that represents a new member of the thymosin–beta family, thymosin β15. Transfection of antisense thymosin β15 constructs into rat prostatic carcinoma cells demonstrates that this molecule positively regulates cell motility, a critical component of the metastatic pathway. Thymosin β15 levels are elevated in human prostate cancer and correlate positively with the Gleason tumor grade. Thymosin β15 may represent a potential new biochemical marker for human prostate cancer progression.
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References
Boring, C.C., Squires, T.S., Tong, T. & Montgomery, S. Cancer statistics, 1994. CA Cancer J. Clin. 44, 7–26 (1994).
Catalona, W.J. et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: Results of a multicenter clinical trial of 6,630 men. J. Urol 151, 1283–1290 (1994).
Cookson, M.S., Floyd, M.K., Ball, T.P. Jr., Miller, E.K. & Sarosdy, M.F. The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels. J. Urol. 154, 1070–1073 (1995).
Aspinall, J.O. et al. Differential expression of apolipoprotein-D and prostate specific antigen in benign and malignant prostate tissues. J. Urol. 154, 622–628 (1995).
Fidler, I.J., Gersten, D.M. & Hart, I.R. The biology of cancer invasion and metastasis. Adv. Cancer Res. 28, 149–250 (1978).
Liotta, L.A. & Kohn, E. Tumor invasion and metastasis: Biochemical mechanisms. Cancer Treat. Res. 40, 223–238 (1988).
Nicolson, G.L. Cancer metastasis: Tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim. Biophys. Acta 948, 175–224 (1988).
Zetter, B.R., Cellular basis of site-specific tumor metastasis. N. Engl. J. Med. 322, 605–612 (1990).
Hosaka, S. Suzuki, M., Goto, M. .& Sato, H. Motility of rat ascites hepatoma cells, with reference to malignant characteristics in cancer metastasis. Gann 69, 273–276 (1978).
Haemmerlin, G. & Strauli, P. In vitro motility of cells from human epidermoid carcinoma: A study by phase-contrast and reflection-contrast cinematography. Int. J. Cancer 27, 603–610 (1981).
Isaacs, J.T., Isaacs, W.B., Feitz, W.F. & Scheres, J. Establishment and characteri zation of seven Dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostate cancers. Prostate 9 261–281 (1986).
Mohler, J.L., Partin, A.W. & Coffey, D.S. Metastatic potential prediction by a visual grading system of cell motility: Prospective validation in the Dunning R-3327 prostatic adenocarcinoma model. Cancer Res. 48, 4312–4317 (1988).
Partin, A.W., Schoeniger, J.S., Mohler, J.L. & Coffey, D.S. Fourier analysis of cell motility: Correlation of motility with metastatic potential. Proc. Natl. Acad. Sci. USA 86, 1254–1258 (1989).
Mohler, J.L. Cellular motility and prostatic carcinoma metastases. Cancer Metast Rev. 12, 53–67 (1993).
Safer, D., Elzinga, M. & Nachmias, V.T. Thymosin β4 and Fx, an actin-sequestering peptide, are indistinguishable. J. Biol. Chem. 266, 4029–4032 (1991).
Yu, F-X., Lin, S.C., Morrison-Bogorad, M. & Yin, H.L. Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins. J. Biol. Chem. 268, 502–509 (1993).
Pantaloni, D. & Carlier, M.F. How profilin promotes actin filament assembly in the presence of thymosin beta 4. Cell 75, 1007–1014 (1993).
Liang, P. & Pardee, A.B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967–971 (1992).
Mihelic, M. & Voelter, W. Distribution and biological activity of β-thymosins. Amino Acids 6, 1–13 (1994).
Freeman, M.R. et al. Culture of a prostatic cell line in basement membrane gels results in an enhancement of malignant properties and constitutive alterations in gene expression. J. Cell. Physiol. 158, 325–336 (1994).
Zhou, B.S., Beidler, D.R. & Cheng, Y.C. Identification of antisense RNA transcripts from a human DNA topoisomerase I pseudogene. Cancer Res. 52, 4280–4285 (1992).
Boyden, S.J. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J. Exp. Med. 115, 453–466 (1962).
Wang, M. & Stearms, M.E. Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in S. C. I. D. mice. Differentiation 48, 115–125 (1991).
Gleason, D.F., Mellinger, G.T. & the Veterans Administration Cooperative Urological Research Group. Prediction of prognosis for prostatic adenocarcinoma by combined histologic grading and clinical staging. J. Urol. 111, 58–64 (1974).
Pienta, K.J. & Coffey, D.S. Cell motility as a chemotherapeutic target. Cancer Surveys 11, 255–263 (1993).
Cunningham, C.C., Stossel, T.P. & Kwiatkowski, D.J. Enhanced motility in NIH 3T3 fibroblasts that overexpress gelsolin. Science 251, 1233–1236 (1991).
Haugwitz, M., Noegel, A.A., Karakesisoglou, J. & Schleicher, M. Dictyostelium amoebae that lack G-actin-sequestering profilins show defects in F-actin content, cytokinesis, and development. Cell 79, 303–314 (1994).
Stossel, T.P. On the crawling of animal cells. Science 260, 1086–1094 (1993).
Hug, C. et al. Capping protein levels influence actin assembly and Cell motility in Dictyostelium. Cell 81, 591–600 (1995).
Bubb, M.R. & Korn, E.D. Kinetic model for the inhibition of actin polymerization by actobindin. Biochemistry 34, 3921–3926 (1995).
Sogani, P.C., Israel, A., Lieberman, P.H., Lesser, M.L. & Whitmore, W.F. Gleason grading of prostate cancer: A predictor of survival. Urology 25, 223–227 (1985).
Chomczynski, P. & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 167, 157–159 (1987).
Galaktionov, K. et al. CD25 phosphatases as potential human oncogenes. Science 269, 1575–1577 (1995).
Kouyama, T. & Mihashi, K. Fluorimetry study of N-(l-pyrenyl)-iodoacetamide-labeled F-actin. Eur. J. Biochem. 114, 33–38 (1981).
Janmey, P.A. et al. Interactions of gelsolin and gelsolin-actin complexes with actin Effects of calcium on actin nucleation, filament severing, and end blocking. Biochemistry 24, 3714–3723 (1985).
Kundra, V., Anand-Apte, B. & Zetter, B.R. The chemotactic response to PDGF-BB: Evidence of a role for ras. J. Cell Biol. 130, 725–731 (1995).
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Bao, L., Loda, M., Janmey, P. et al. Thymosin β15: A novel regulator of tumor cell motility upregulated in metastatic prostate cancer. Nat Med 2, 1322–1328 (1996). https://doi.org/10.1038/nm1296-1322
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DOI: https://doi.org/10.1038/nm1296-1322
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