A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells

J. F. Novak, M. B. Judkins, M. I. Chernin, P. Cassoni, G. Bussolati, J. A. Nitche, Satoru Nishimoto

Research output: Contribution to journalArticle

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Abstract

We have previously described the presence of the functional plasminogen activator system on the surfaces of bone neoplastic cells and the fact that plasmin specifically cleaves bone matrix protein osteocalcin (OC). The cleavage of OC to NH2-midterminal (1-44) and COOH-terminal RFYGPV hexapeptide (44-49) proceeds with detachment of both products from bone mineral. Because the sequence of OC-derived hexapeptide (HP) is nearly identical to the E2 region of the oxytocin receptor (OTR), we set out to ascertain whether the HP interferes with the osteosarcoma (OS)-associated oxytocin (OT) system. We documented the presence and functional activity of OTRs in several OS cells by means of (a) OT-mediated inhibition of OS growth; (b) expression of OTR mRNA by means of reverse transcription-PCR; (c) immunofluorescence staining with IF3 monoclonal antibody specific for human OTR; and (d) saturation binding and Scatchard analysis of OT binding to the receptors of isolated membranes or intact OS cells. Although we could not demonstrate direct binding of HP to OT, the presence of HP in cultures of OS cells antagonizes the inhibitory effect of OT on these cells. Additionally, in competitive binding assays, the HP effectively competes with binding of OT to its cognate receptors. The results indicate the existence of an OTR/OT system in tumor cells of bone origin. Suggested plasminogen activator-OC- OTR/OT interactions may have an effect on the regulation of cell proliferation within the bone tissue as well as properties of the extracellular matrix surrounding the tumor foci in the bone.

Original languageEnglish (US)
Pages (from-to)3470-3476
Number of pages7
JournalCancer Research
Volume60
Issue number13
StatePublished - Jul 1 2000

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Fibrinolysin
Osteocalcin
Oxytocin
Osteosarcoma
Oxytocin Receptors
Growth
Bone and Bones
Plasminogen Activators
Bone Matrix
Competitive Binding
Reverse Transcription
Fluorescent Antibody Technique
Extracellular Matrix
Minerals
Neoplasms
Cell Culture Techniques
Monoclonal Antibodies
Cell Proliferation
Staining and Labeling
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Novak, J. F., Judkins, M. B., Chernin, M. I., Cassoni, P., Bussolati, G., Nitche, J. A., & Nishimoto, S. (2000). A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells. Cancer Research, 60(13), 3470-3476.

A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells. / Novak, J. F.; Judkins, M. B.; Chernin, M. I.; Cassoni, P.; Bussolati, G.; Nitche, J. A.; Nishimoto, Satoru.

In: Cancer Research, Vol. 60, No. 13, 01.07.2000, p. 3470-3476.

Research output: Contribution to journalArticle

Novak, JF, Judkins, MB, Chernin, MI, Cassoni, P, Bussolati, G, Nitche, JA & Nishimoto, S 2000, 'A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells', Cancer Research, vol. 60, no. 13, pp. 3470-3476.
Novak JF, Judkins MB, Chernin MI, Cassoni P, Bussolati G, Nitche JA et al. A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells. Cancer Research. 2000 Jul 1;60(13):3470-3476.
Novak, J. F. ; Judkins, M. B. ; Chernin, M. I. ; Cassoni, P. ; Bussolati, G. ; Nitche, J. A. ; Nishimoto, Satoru. / A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth of inhibition of osteosarcoma cells. In: Cancer Research. 2000 ; Vol. 60, No. 13. pp. 3470-3476.
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