The Multifaceted Actions of PTHrP in Skeletal Metastasis

Soki, Fabiana N.; Park, Serk In; McCauley, Laurie K.

doi:10.2217/fon.12.76

Cited by 95 publications

(87 citation statements)

References 99 publications

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“…PTHrP expression is commonly found in many types of cancers, including the breast, and it can promote tumor growth and metastasis (67,68). While PTH and PTHrP have similar binding affinities to the G protein-coupled PTH1R, PTH binds with greater stability than the PTHrP, facilitating prolonged signaling even after internalization of the ligand-receptor complex, resulting in different downstream effects (69).…”

Section: Discussionmentioning

confidence: 99%

Prevention of breast cancer skeletal metastases with parathyroid hormone

Swami¹,

Johnson²,

Bettinson³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Prevention of breast cancer skeletal metastases with parathyroid hormone

Swami¹,

Johnson²,

Bettinson³

et al. 2017

JCI Insight

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“…RANKL binds the RANK receptor on osteoclast precursors and promotes osteoclastogenesis. In turn, bone resorption by osteoclasts releases other peptides which can promote tumor growth (i.e., TGF-β, IGFs and PDGF) [22]. PTH can also stimulate the osteoblast niche within the bone marrow.…”

Section: Why Is the Effect Of Adjuvant Clodronate Not Inferior When Cmentioning

confidence: 99%

“…PTH is similar to PTH-related peptide (PTHrp) and both PTHrp and PTH share the same receptor (PTHR1) which is expressed on different types of cancers. The interaction of PTH/PTHrp with PTHR1 can promote cell proliferation and growth, resistance to apoptosis, invasion and metastasis [22]. Of note, a post hoc analysis of a randomized placebo-controlled trial evaluating zoledronic acid for metastatic prostate cancer reported that elevated serum PTH levels could predict worse outcomes in patients treated with zoledronic acid [25].…”

Section: Why Is the Effect Of Adjuvant Clodronate Not Inferior When Cmentioning

confidence: 99%

Adjuvant Bisphosphonates in Patients with Breast Cancer: Does the Potency Matter?

Amoroso¹,

Petrelli²,

Pedersini³

et al. 2015

Future Oncol.

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Keywords• bisphosphonates • breast cancer • disseminated tumor cells • osteoblastic niche • parathyroid hormone Breast cancer is the malignancy with the highest incidence in females, and patient clinical outcomes are steadily improving during the last decades. Early detection and advances in adjuvant therapies are the possible explanations for the observed mortality reduction.The rationale for administering adjuvant systemic therapies in women with radically operated breast cancer is to eradicate micrometastases that are supposed to be present at the time of surgery. Disseminated tumor cells (DTCs) from breast cancer and other solid tumors can colonize the bone early during the disease course. DTCs directly compete with hematopoietic stem cells for occupancy of the osteoblastic niches in the bone marrow [1]. Since this niche allows DTCs to evade systemic anticancer therapies, the bone marrow is both a storehouse and a sanctuary for these cells that lay dormant for a considerable period of time before becoming active and able to metastasize to skeletal and extraskeletal sites [1].Cytokines and growth factors derived from the bone microenvironment modulate the activity of DTCs in the osteoblastic niche [2].Bisphosphonates (BPs) are analogs of pyrophosphates that can inhibit osteoclast-mediated bone resorption. As a result, BPs deprive the bone microenvironment of bone-derived growth factors that are required for seeding and growth in the bone marrow [3]. The use of these drugs in patients with early breast cancer may render the bone microenvironment less fertile for metastatic tumor growth and prolong the dormant state of DTCs within their niche. Evidence of efficacy of BPs in early-stage breast cancerSeveral randomized clinical trials have evaluated the efficacy of BPs administered in adjuvant setting in addition to chemotherapy and endocrine therapy with c onflicting results [3].Whenever the evidence is not definitive, clinical researchers increasingly rely on systematic reviews and meta-analyses to estimate the effect size of a particular treatment in a defined disease setting. Ben-Aharon et al. reported no significant difference in either disease-free survival (DFS) or overall survival (OS) in a pooled analysis of 13 randomized trials evaluating adjuvant BPs (hazard ratio [HR] of DFS: 0.95; 95% CI: 0.81-1.12; HR of OS: 0.89; 95% CI: 0.79-1.01) [4]. This literature-based meta-analysis, however, demonstrated a positive effect on DFS for

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“…The PTHrP protein is a polyhormone with multiple biologically active domains conferring different actions as an autocrine, paracrine, endocrine, and intracrine hormone [Soki et al, 2012]. It has many biological actions during fetal growth and development and throughout life [Strewler, 2000].…”

Section: Introductionmentioning

confidence: 99%

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

Thomas‐Teinturier

Pereda

Garin

et al. 2015

American J of Med Genetics Pt A

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Autosomal-dominant brachydactyly type E is a congenital limb malformation characterized by small hands and feet as a result of shortened metacarpals and metatarsals. Alterations that predict haploinsufficiency of PTHLH, the gene coding for parathyroid hormone related protein (PTHrP), have been identified as a cause of this disorder in seven families. Here, we report three patients affected with brachydactyly type E, caused by PTHLH mutations expected to result in haploinsufficiency, and discuss our data compared to published reports.

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The Multifaceted Actions of PTHrP in Skeletal Metastasis

Cited by 95 publications

References 99 publications

Prevention of breast cancer skeletal metastases with parathyroid hormone

Prevention of breast cancer skeletal metastases with parathyroid hormone

Adjuvant Bisphosphonates in Patients with Breast Cancer: Does the Potency Matter?

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

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