Expression and In Vitro Modification of Parathyroid Hormone-Related Protein (PTHrP) and PTH/PTHrP-Receptor in Human Myeloma Cells

To elucidate the role of PTHrP in myeloma, we examined the expression levels of PTHrP and its receptor in human myeloma cell lines and clinical specimens from 13 myeloma cases. In vitro modification of PTHrP expression and production induced by TGF-β and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six out of seven myeloma cell lines with an inverse correlation with the expression of its receptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHrP expression and secretion into culture medium were enhanced by supplemental TGF-β and PMA. PMA also seemed to affect PTHrP upregulation via TGF-β activation. The fundamental role of PTHrP in bone lesions and hypercalcemia in myeloma may be important to consider even during the initial phase of the disease and particularly in the progression of bone complications with hypercalcemia.

[1]  H. Drexler,et al.  Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia. , 2000, Leukemia research.

[2]  K. Orita,et al.  Human bone marrow stroma‐dependent cell line MOLP‐5 derived from a patient in leukaemic phase of multiple myeloma , 2000, British journal of haematology.

[3]  M. Kurosumi,et al.  Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6 , 1999, British Journal of Cancer.

[4]  H. Saisho,et al.  Significance of parathyroid hormone‐related protein as a factor stimulating bone resorption and causing hypercalcemia in myeloma , 1998, American journal of hematology.

[5]  T. Martin,et al.  Parathyroid Hormone‐Related Protein mRNA and Protein Expression in Multiple Myeloma: A Case Report , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  A. Takaori-Kondo,et al.  Parathyroid hormone-related protein-induced hypercalcemia in SCID mice engrafted with adult T-cell leukemia cells. , 1998, Blood.

[7]  M. Taniwaki,et al.  A novel mature B‐cell line (DOBIL‐6) producing both parathyroid hormone‐related protein and interleukin‐6 from a myeloma patient presenting with hypercalcaemia , 1998, British journal of haematology.

[8]  P. Esbrit,et al.  Parathyroid hormone-related protein increases DNA synthesis in proximal tubule cells by cyclic AMP- and protein kinase C-dependent pathways. , 1998, Life sciences.

[9]  M. Taniwaki,et al.  Establishment of a new human myeloma cell line, KMS-18, having t(4;14)(p16.3;q32.3) derived from a case phenotypically transformed from Ig A-lambda to BJP-lambda, and associated with hyperammonemia. , 1998, International journal of oncology.

[10]  K. Orita,et al.  A novel ALL-L3 cell line, BALM-16, lacking expression of immunoglobulin chains derived from a patient with hypercalcemia , 1997, Leukemia.

[11]  G. Roodman.  Mechanisms of bone lesions in multiple myeloma and lymphoma , 1997, Cancer.

[12]  M. Mori,et al.  Raised plasma concentrations of parathyroid hormone related peptide in hypercalcemic multiple myeloma. , 1997, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[13]  T. Guise,et al.  Hypercalcemia of Malignancy , 1987 .

[14]  H. Uemura,et al.  Effects of Transforming Growth Factor‐β on the Production of Parathyroid Hormone‐Related Peptide in a Human Ovarian Cancer Cell Line in vitro , 1997 .

[15]  H. Kurabayashi,et al.  Ultrastructure of myeloma cells producing parathyroid hormone-related peptide. , 1997, Clinical and laboratory haematology.

[16]  M. Oken.  Multiple myeloma: prognosis and standard treatment. , 1997, Cancer investigation.

[17]  H. Uemura,et al.  Effects of transforming growth factor-beta on the production of parathyroid hormone-related peptide in a human ovarian cancer cell line in vitro. , 1997, The journal of obstetrics and gynaecology research.

[18]  D. Goltzman,et al.  Parathyroid hormone-related peptide and hypercalcemia of malignancy. , 1997, Cancer treatment and research.

[19]  J. Kurebayashi,et al.  Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells. , 1997, British Journal of Cancer.

[20]  M. Namba,et al.  Down regulation of protein kinase C during growth enhancement induced by interleukin-6 on a human myeloma cell line, KMS-11. , 1996, Cancer letters.

[21]  T. Martin,et al.  Parathyroid hormone‐related protein in hypercalcaemia associated with haematological malignancy , 1996, British journal of haematology.

[22]  S. Dower,et al.  Modulation of osteoclast-activating factor activity of multiple myeloma bone marrow cells by different interleukin-1 inhibitors. , 1996, Experimental hematology.

[23]  M. Kurosumi,et al.  A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice. , 1996, British Journal of Cancer.

[24]  R. Kremer,et al.  Parathyroid-hormone-related peptide in hematologic malignancies. , 1996, The American journal of medicine.

[25]  S. Mizutani,et al.  Establishment and characterization of a novel cell line, TK-6, derived from T cell blast crisis of chronic myelogenous leukemia, with the secretion of parathyroid hormone-related protein. , 1995, Leukemia.

[26]  S. Eto,et al.  Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro. , 1995, Blood.

[27]  M. Kurosumi,et al.  A new human breast cancer cell line, KPL-1 secretes tumour-associated antigens and grows rapidly in female athymic nude mice. , 1995, British Journal of Cancer.

[28]  T. Martin,et al.  Evidence for the synthesis of parathyroid hormone-related protein (PTHrP) by nontransformed clonal rat osteoblastic cells in vitro. , 1995, Bone.

[29]  H. Shibata,et al.  Evidence for parathyroid hormone-related peptide as a cause of hypercalcemia in myeloma. , 1994, Blood.

[30]  T. Rosol,et al.  Transforming growth factor-β 1 regulates steady-state PTH/PTHrP receptor mRNA levels and PTHrP binding in ROS 17/2.8 osteosarcoma cells , 1994, Molecular and Cellular Endocrinology.

[31]  M. Fukumoto,et al.  Production of parathyroid hormone‐related protein by cultured human myeloma cells , 1994, American journal of hematology.

[32]  E. Ejima,et al.  Hypercalcemia, parathyroid hormone-related protein expression and human T-cell leukemia virus infection. , 1994, Leukemia & lymphoma.

[33]  T. Rosol,et al.  Regulation of parathyroid hormone-related protein production by a squamous carcinoma cell line in vitro. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[34]  K. Chihara,et al.  Involvement of dual signal transduction systems in the stimulation of osteoclast-like cell formation by parathyroid hormone and parathyroid hormone-related peptide. , 1993, Biochemical and biophysical research communications.

[35]  F. caligaris-Cappio,et al.  Bone marrow microenvironment and the progression of multiple myeloma. , 1992, Leukemia & lymphoma.

[36]  T. Sugihara,et al.  Two human myeloma cell lines, amylase‐producing KMS‐12‐PE and amylase‐non‐producing KMS‐12‐BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32) , 1989, British journal of haematology.

[37]  K. Miyamoto,et al.  Establishment and characterization of a human myeloma cell line (KMM‐1) , 1982, Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society.