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Gene Review

PTN  -  pleiotrophin

Homo sapiens

Synonyms: HARP, HB-GAM, HBBM, HBGF-8, HBGF8, ...
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Disease relevance of PTN

  • Here, we report on the presence and purification of two naturally occurring forms of PTN (18 and 15 kDa) that differentially promote glioblastoma migration and proliferation [1].
  • In contrast, samples from patients with pyogenic arthritis had moderate PTN levels, and those from patients with osteoarthritis had only a slight increase in PTN, as measured by ELISA [2].
  • Our findings suggest that upregulated expression of PTN and PTPzeta/RPTPbeta in human astrocytic tumor cells can create an autocrine loop that is important for glioma cell migration [3].
  • PTN immunoreactivity as determined by ELISA and immunohistochemistry analysis was increased in low-grade astrocytomas compared to normal brain [3].
  • Pleiotrophin (PTN) is a developmentally regulated protein that has been shown to be involved in tumor growth and metastasis presumably by activating tumor angiogenesis [4].

Psychiatry related information on PTN


High impact information on PTN

  • We now demonstrate that PTN disrupts cytoskeletal protein complexes, ablates calcium-dependent homophilic cell-cell adhesion, stimulates ubiquitination and degradation of N-cadherin, reorganizes the actin cytoskeleton, and induces a morphological epithelial-mesenchymal transition (EMT) in PTN-stimulated U373 cells [7].
  • Furthermore, we demonstrate that PTN stimulates the degradation of beta-adducin in PTN-stimulated cells [8].
  • We have found that PTN binds to and functionally inactivates the catalytic activity of RPTP beta/zeta [9].
  • Pleiotrophin (PTN) is a platelet-derived growth factor-inducible, 18-kDa heparin-binding cytokine that signals diverse phenotypes in normal and deregulated cellular growth and differentiation [9].
  • The autocrine function of PTN was confirmed by using PTN-binding antibodies that inhibited the proliferation rate by 50% in Colo357 cells but also in a different pancreatic cancer cell line, Panc89 [10].

Chemical compound and disease context of PTN

  • Using subtractive cloning combined with cDNA array analysis, we previously identified the genes encoding for the protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal brain [3].
  • The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells [11].
  • In contrast, the appican CS from SH-SY5Y neuroblastoma cells contained no E disaccharide and showed no binding to either MK or PTN [12].
  • In this study, the appican CS chain from rat C6 glioma cells was shown to specifically bind several growth/differentiation factors including midkine (MK) and pleiotrophin (PTN) [12].
  • Here, we describe a strategy to inhibit pleiotrophin (PTN), a heparin-binding autocrine growth factor for melanoma cells [13].

Biological context of PTN


Anatomical context of PTN


Associations of PTN with chemical compounds


Regulatory relationships of PTN


Other interactions of PTN

  • Recent reports of ALK expression in a range of carcinoma-derived cell lines together with its apparent role as a receptor for PTN and MK, both of which have been implicated in tumourigenesis, raise the possibility that ALK-mediated signalling could play a role in the development and/or progression of a number of common solid tumours [23].
  • However, PTN levels were significantly associated with those of fibroblast growth factor-2, suggesting co-regulation of both factors [3].
  • Full-length HB-GAM is not a mitogen for Balb/3T3 clone A31, Balb MK, NRK, or human umbilical vein endothelial cells [24].
  • Nevertheless, proteoglycans might play a role in the concentration of PTN on the cell surface for a more efficient interaction with nucleolin [11].
  • The N-terminal sequence was homologous to HB-GAM/PTN, and polymerase chain reaction amplification and DNA sequencing confirmed that the respective transcript was present in the cancer cells [25].

Analytical, diagnostic and therapeutic context of PTN


  1. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. Lu, K.V., Jong, K.A., Kim, G.Y., Singh, J., Dia, E.Q., Yoshimoto, K., Wang, M.Y., Cloughesy, T.F., Nelson, S.F., Mischel, P.S. J. Biol. Chem. (2005) [Pubmed]
  2. Expression of pleiotrophin, an embryonic growth and differentiation factor, in rheumatoid arthritis. Pufe, T., Bartscher, M., Petersen, W., Tillmann, B., Mentlein, R. Arthritis Rheum. (2003) [Pubmed]
  3. Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas. Ulbricht, U., Brockmann, M.A., Aigner, A., Eckerich, C., Müller, S., Fillbrandt, R., Westphal, M., Lamszus, K. J. Neuropathol. Exp. Neurol. (2003) [Pubmed]
  4. Pleiotrophin induces angiogenesis: involvement of the phosphoinositide-3 kinase but not the nitric oxide synthase pathways. Souttou, B., Raulais, D., Vigny, M. J. Cell. Physiol. (2001) [Pubmed]
  5. Midkine and pleiotrophin in neural development and cancer. Kadomatsu, K., Muramatsu, T. Cancer Lett. (2004) [Pubmed]
  6. Defining anticipatory nausea and vomiting: differences among cancer chemotherapy patients who report pretreatment nausea. Andrykowski, M.A. Journal of behavioral medicine. (1988) [Pubmed]
  7. Pleiotrophin disrupts calcium-dependent homophilic cell-cell adhesion and initiates an epithelial-mesenchymal transition. Perez-Pinera, P., Alcantara, S., Dimitrov, T., Vega, J.A., Deuel, T.F. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Pleiotrophin regulates serine phosphorylation and the cellular distribution of beta-adducin through activation of protein kinase C. Pariser, H., Herradon, G., Ezquerra, L., Perez-Pinera, P., Deuel, T.F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Meng, K., Rodriguez-Peña, A., Dimitrov, T., Chen, W., Yamin, M., Noda, M., Deuel, T.F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Pleiotrophin can be rate-limiting for pancreatic cancer cell growth. Weber, D., Klomp, H.J., Czubayko, F., Wellstein, A., Juhl, H. Cancer Res. (2000) [Pubmed]
  11. Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin. Said, E.A., Courty, J., Svab, J., Delbé, J., Krust, B., Hovanessian, A.G. FEBS J. (2005) [Pubmed]
  12. Chondroitin sulfate of appican, the proteoglycan form of amyloid precursor protein, produced by C6 glioma cells interacts with heparin-binding neuroregulatory factors. Umehara, Y., Yamada, S., Nishimura, S., Shioi, J., Robakis, N.K., Sugahara, K. FEBS Lett. (2004) [Pubmed]
  13. An antisense strategy for inhibition of human melanoma growth targets the growth factor pleiotrophin. Satyamoorthy, K., Oka, M., Herlyn, M. Pigment Cell Res. (2000) [Pubmed]
  14. Effects of pleiotrophin, a heparin-binding growth factor, on human primary and immortalized chondrocytes. Pufe, T., Groth, G., Goldring, M.B., Tillmann, B., Mentlein, R. Osteoarthr. Cartil. (2007) [Pubmed]
  15. Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1. Hashimoto-Gotoh, T., Ohnishi, H., Tsujimura, A., Tsunezuka, H., Imai, K., Masuda, H., Nakamura, T. J. Bone Miner. Metab. (2004) [Pubmed]
  16. Fyn is a downstream target of the pleiotrophin/receptor protein tyrosine phosphatase beta/zeta-signaling pathway: regulation of tyrosine phosphorylation of Fyn by pleiotrophin. Pariser, H., Ezquerra, L., Herradon, G., Perez-Pinera, P., Deuel, T.F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  17. Pleiotrophin induces formation of functional neovasculature in vivo. Christman, K.L., Fang, Q., Kim, A.J., Sievers, R.E., Fok, H.H., Candia, A.F., Colley, K.J., Herradon, G., Ezquerra, L., Deuel, T.F., Lee, R.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  18. Isolation from bovine brain and structural characterization of HBNF, a heparin-binding neurotrophic factor. Böhlen, P., Müller, T., Gautschi-Sova, P., Albrecht, U., Rasool, C.G., Decker, M., Seddon, A., Fafeur, V., Kovesdi, I., Kretschmer, P. Growth Factors (1991) [Pubmed]
  19. Refolding and characterization of human recombinant heparin-binding neurite-promoting factor. Seddon, A.P., Hulmes, J.D., Decker, M.M., Kovesdi, I., Fairhurst, J.L., Backer, J., Dougher-Vermazen, M., Böhlen, P. Protein Expr. Purif. (1994) [Pubmed]
  20. Neurite outgrowth in brain neurons induced by heparin-binding growth-associated molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan sulfate at the cell surface. Kinnunen, T., Raulo, E., Nolo, R., Maccarana, M., Lindahl, U., Rauvala, H. J. Biol. Chem. (1996) [Pubmed]
  21. Reciprocal expression of pleiotrophin and midkine in normal versus malignant lung tissues. Garver, R.I., Chan, C.S., Milner, P.G. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
  22. HBNF and MK, members of a novel gene family of heparin-binding proteins with potential roles in embryogenesis and brain function. Böhlen, P., Kovesdi, I. Prog. Growth Factor Res. (1991) [Pubmed]
  23. Anaplastic lymphoma kinase proteins in growth control and cancer. Pulford, K., Morris, S.W., Turturro, F. J. Cell. Physiol. (2004) [Pubmed]
  24. Structural and functional characterization of full-length heparin-binding growth associated molecule. Hampton, B.S., Marshak, D.R., Burgess, W.H. Mol. Biol. Cell (1992) [Pubmed]
  25. A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine. Wellstein, A., Fang, W.J., Khatri, A., Lu, Y., Swain, S.S., Dickson, R.B., Sasse, J., Riegel, A.T., Lippman, M.E. J. Biol. Chem. (1992) [Pubmed]
  26. Significance of the expression of the growth factor pleiotrophin in pancreatic cancer patients. Klomp, H.J., Zernial, O., Flachmann, S., Wellstein, A., Juhl, H. Clin. Cancer Res. (2002) [Pubmed]
  27. Mechanical regulation of HB-GAM expression in bone cells. Liedert, A., Augat, P., Ignatius, A., Hausser, H.J., Claes, L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  28. Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins. Kretschmer, P.J., Fairhurst, J.L., Decker, M.M., Chan, C.P., Gluzman, Y., Böhlen, P., Kovesdi, I. Growth Factors (1991) [Pubmed]
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