PMID- 23787729
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20131220
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 29
IP  - 1
DP  - 2014 Jan
TI  - PTHrP produced by myeloma plasma cells regulates their survival and 
      pro-osteoclast activity for bone disease progression.
PG  - 55-66
LID - 10.1002/jbmr.2022 [doi]
AB  - To promote their survival and progression in the skeleton, osteotropic 
      malignancies of breast, lung, and prostate produce parathyroid hormone-related 
      protein (PTHrP), which induces hypercalcemia. PTHrP serum elevations have also 
      been described in multiple myeloma (MM), although their role is not well defined. 
      When we investigated MM cells from patients and cell lines, we found that PTHrP 
      and its receptor (PTH-R1) are highly expressed, and that PTHrP is secreted both 
      as a full-length molecule and as small subunits. Among these subunits, the 
      mid-region, including the nuclear localization sequence (NLS), exerted a 
      proliferative effect because it was accumulated in nuclei of MM cells surviving 
      in starvation conditions. This was confirmed by increased transcription of 
      several genes enrolled in proliferation and apoptosis control. PTHrP was also 
      found to stimulate PTH-R1 in MM cells. PTH-R1's selective activation by the 
      full-length PTHrP molecule or the NH2 -terminal fragment resulted in a 
      significant increase of intracellular Ca(2+) influx, cyclic adenosine 
      monophosphate (cAMP) content, and expression of receptor activator of NF-kappaB 
      ligand (RANKL) and monocyte chemoattractant protein-1 (MCP-1). Our data 
      definitely clarify the role of PTHrP in MM. The PTHrP peptide is functionally 
      secreted by malignant plasma cells and contributes to MM tumor biology and 
      progression, both by intracrine maintenance of cell proliferation in stress 
      conditions and by autocrine or paracrine stimulation of PTH-R1, which in turn 
      reinforces the production of osteoclastogenic factors. (c) 2014 American Society 
      for Bone and Mineral Research.
CI  - (c) 2014 American Society for Bone and Mineral Research.
FAU - Cafforio, Paola
AU  - Cafforio P
AD  - Department of Biomedical Sciences and Human Oncology, Section of Internal 
      Medicine and Oncology, University of Bari "Aldo Moro,", Bari, Italy.
FAU - Savonarola, Annalisa
AU  - Savonarola A
FAU - Stucci, Stefania
AU  - Stucci S
FAU - De Matteo, Monica
AU  - De Matteo M
FAU - Tucci, Marco
AU  - Tucci M
FAU - Brunetti, Anna Elisabetta
AU  - Brunetti AE
FAU - Vecchio, Vita Mariagrazia
AU  - Vecchio VM
FAU - Silvestris, Francesco
AU  - Silvestris F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Parathyroid Hormone-Related Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptor, Parathyroid Hormone, Type 1)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Chemokine CCL2/biosynthesis
MH  - Cyclic AMP/metabolism
MH  - Disease Progression
MH  - Humans
MH  - Multiple Myeloma/*metabolism
MH  - Parathyroid Hormone-Related Protein/*biosynthesis
MH  - Peptide Fragments/biosynthesis/pharmacology
MH  - Plasma Cells/*metabolism
MH  - Receptor Activator of Nuclear Factor-kappa B/biosynthesis
MH  - Receptor, Parathyroid Hormone, Type 1/*biosynthesis/metabolism
OTO - NOTNLM
OT  - CELL SURVIVAL
OT  - MULTIPLE MYELOMA
OT  - NLS REGION
OT  - OSTEOCLASTOGENESIS
OT  - PTHRP
EDAT- 2013/06/22 06:00
MHDA- 2014/08/20 06:00
CRDT- 2013/06/22 06:00
PHST- 2013/03/07 00:00 [received]
PHST- 2013/05/31 00:00 [revised]
PHST- 2013/06/10 00:00 [accepted]
PHST- 2013/06/22 06:00 [entrez]
PHST- 2013/06/22 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
AID - 10.1002/jbmr.2022 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2014 Jan;29(1):55-66. doi: 10.1002/jbmr.2022.