-
International Journal of Molecular... Sep 2020The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone... (Review)
Review
The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.
Topics: Animals; Bone Neoplasms; Humans; Neoplasm Metastasis; Osteosarcoma; Signal Transduction; Tumor Microenvironment
PubMed: 32977425
DOI: 10.3390/ijms21196985 -
Cancer Letters Apr 2022During disease progression from primary towards metastatic prostate cancer (PCa), and in particular bone metastases, the tumor microenvironment (TME) evolves in parallel... (Review)
Review
During disease progression from primary towards metastatic prostate cancer (PCa), and in particular bone metastases, the tumor microenvironment (TME) evolves in parallel with the cancer clones, altering extracellular matrix composition (ECM), vasculature architecture, and recruiting specialized tumor-supporting cells that favor tumor spread and colonization at distant sites. We introduce the clinical profile of advanced metastatic PCa in terms of common genetic alterations. Findings from recently developed models of PCa metastatic spread are discussed, focusing mainly on the role of the TME (mainly matrix and fibroblast cell types), at distinct stages: premetastatic niche orchestrated by the primary tumor towards the metastatic site and bone metastasis. We report evidence of premetastatic niche formation, such as the mechanisms of distant site conditioning by extracellular vesicles, chemokines and other tumor-derived mechanisms, including altered cancer cell-ECM interactions. Furthermore, evidence supporting the similarities of stroma alterations among the primary PCa and bone metastasis, and contribution of TME to androgen deprivation therapy resistance are also discussed. We summarize the available bone metastasis transgenic mouse models of PCa from a perspective of pro-metastatic TME alterations during disease progression and give an update on the current diagnostic and therapeutic radiological strategies for bone metastasis clinical management.
Topics: Animals; Bone Neoplasms; Disease Progression; Male; Neoplasm Metastasis; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 35051532
DOI: 10.1016/j.canlet.2022.01.015 -
Cells Jun 2021Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone... (Review)
Review
Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient's survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients' survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.
Topics: Bone Neoplasms; Bone Resorption; Breast Neoplasms; Disease-Free Survival; Female; Humans; Neoplasm Metastasis; Survival Rate; Tumor Microenvironment
PubMed: 34199522
DOI: 10.3390/cells10061377 -
Nature Reviews. Cancer Feb 2022Many cancer types metastasize to bone. This propensity may be a product of genetic traits of the primary tumour in some cancers. Upon arrival, cancer cells establish... (Review)
Review
Many cancer types metastasize to bone. This propensity may be a product of genetic traits of the primary tumour in some cancers. Upon arrival, cancer cells establish interactions with various bone-resident cells during the process of colonization. These interactions, to a large degree, dictate cancer cell fates at multiple steps of the metastatic cascade, from single cells to overt metastases. The bone microenvironment may even influence cancer cells to subsequently spread to multiple other organs. Therefore, it is imperative to spatiotemporally delineate the evolving cancer-bone crosstalk during bone colonization. In this Review, we provide a summary of the bone microenvironment and its impact on bone metastasis. On the basis of the microscopic anatomy, we tentatively define a roadmap of the journey of cancer cells through bone relative to various microenvironment components, including the potential of bone to function as a launch pad for secondary metastasis. Finally, we examine common and distinct features of bone metastasis from various cancer types. Our goal is to stimulate future studies leading to the development of a broader scope of potent therapies.
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 34611349
DOI: 10.1038/s41568-021-00406-5 -
Pediatric Radiology Aug 2022Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of... (Review)
Review
Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of the cases, is now recognized to be a true neoplasm, whereas ABC-like changes associated to other bone neoplasms (also referred in the literature as secondary ABC) accounts for the remaining 30%. The solid variant of ABC is also considered a true neoplasm but is rare. ABC can involve any bone in the body, and although it has a metaphyseal preference, it can involve any part of a bone and soft tissues. As with any bone tumor, the initial evaluation of ABCs should be done with radiographs followed by magnetic resonance imaging or less frequently computed tomography for further characterization. The imaging appearance of ABC is variable; however, a lytic and expansile lesion with fluid-fluid levels is the most common presentation. The main differential diagnosis of an ABC in the pediatric population is unicameral bone cyst (UBC) and telangiectatic osteosarcoma, therefore a biopsy is recommended before treatment. The therapeutic options of ABC range from curettage with or without adjuncts such as phenol, liquid nitrogen, argon laser and bone grafting or bone substitutes to more recently employed alternatives such as image-guided sclerotherapy with various sclerosing agents and monoclonal antibodies (e.g., Denosumab).
Topics: Bone Cysts; Bone Cysts, Aneurysmal; Bone Neoplasms; Child; Humans; Osteosarcoma; Tomography, X-Ray Computed; Young Adult
PubMed: 35941207
DOI: 10.1007/s00247-022-05396-6 -
Biomedical Engineering Online Mar 2021Osteosarcoma (OS) is the most common primary bone malignancy that affects children and young adults. OS is characterized by a high degree of malignancy, strong... (Review)
Review
Osteosarcoma (OS) is the most common primary bone malignancy that affects children and young adults. OS is characterized by a high degree of malignancy, strong invasiveness, rapid disease progression, and extremely high mortality rate; it is considered as a serious threat to the human health globally. The incidence of OS is common in the metaphysis of long tubular bones, but rare in the spine, pelvis, and sacrum areas; moreover, majority of the OS patients present with only a single lesion. OS has a bimodal distribution pattern, that is, its incidence peaks in the second decade of life and in late adulthood. We examine historical and current literature to present a succinct review of OS. In this review, we have discussed the types, clinical diagnosis, and modern and future treatment methods of OS. The purpose of this article is to inspire new ideas to develop more effective therapeutic options.
Topics: Antineoplastic Agents; Bone Neoplasms; Disease Progression; Genetic Therapy; Humans; Immunotherapy; Magnetic Resonance Imaging; Neoplasm Staging; Osteosarcoma; Radiotherapy; Tomography, X-Ray Computed
PubMed: 33653371
DOI: 10.1186/s12938-021-00860-0 -
Critical Reviews in Oncology/hematology Oct 2021Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This... (Review)
Review
BACKGROUND
Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases.
METHODS
MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched to July 16, 2020.
RESULTS
A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n = 4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n = 16, 94%) and were delivered by qualified exercise professionals (n = 13, 76%).
CONCLUSIONS
Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction.
Topics: Bone Neoplasms; Exercise; Exercise Therapy; Humans; Quality of Life
PubMed: 34358650
DOI: 10.1016/j.critrevonc.2021.103433 -
Cell Proliferation Feb 2021Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and... (Review)
Review
Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and survival. STAT proteins are conserved among eukaryotes and are important for biological functions of embryogenesis, immunity, haematopoiesis and cell migration. STAT3 is widely expressed and located in the cytoplasm in an inactive form. STAT3 is rapidly and transiently activated by tyrosine phosphorylation by a range of signalling pathways, including cytokines from the IL-6 family and growth factors, such as EGF and PDGF. STAT3 activation and subsequent dimer formation initiates nuclear translocation of STAT3 for the regulation of target gene transcription. Four STAT3 isoforms have been identified, which have distinct biological functions. STAT3 is considered a proto-oncogene and constitutive activation of STAT3 is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas. In this review, we focus on recent progress on STAT3 and osteosarcoma (OS). Notably, STAT3 is overexpressed and associated with the poor prognosis of OS. Constitutive activation of STAT3 in OS appears to upregulate the expression of target oncogenes, leading to OS cell transformation, proliferation, tumour formation, invasion, metastasis, immune evasion and drug resistance. Taken together, STAT3 is a target for cancer therapy, and STAT3 inhibitors represent potential therapeutic candidates for the treatment of OS.
Topics: Bone Neoplasms; Cytokines; Drug Resistance, Neoplasm; Enzyme Inhibitors; Humans; Neoplasm Metastasis; Osteosarcoma; Prognosis; Protein Isoforms; Proto-Oncogene Mas; STAT3 Transcription Factor
PubMed: 33382511
DOI: 10.1111/cpr.12974 -
International Journal of Molecular... Jul 2020Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after... (Review)
Review
Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Osteosarcoma; Signal Transduction; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 32717819
DOI: 10.3390/ijms21155207 -
The Journal of Clinical Investigation Jul 2020Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with...
Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1-/-) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compared with WT mice, Pd1-/- mice exhibited increased baseline pain sensitivity, but the development of bone cancer pain was compromised in Pd1-/- mice. Consistently, these beneficial effects in Pd1-/- mice were recapitulated by repeated i.v. applications of nivolumab in WT mice, even though nivolumab initially increased mechanical and thermal pain. Notably, PD-1 deficiency or nivolumab treatment inhibited osteoclastogenesis without altering tumor burden. PD-L1 and CCL2 are upregulated within the local tumor microenvironment, and PD-L1 promoted RANKL-induced osteoclastogenesis through JNK activation and CCL2 secretion. Bone cancer upregulated CCR2 in primary sensory neurons, and CCR2 antagonism effectively reduced bone cancer pain. Our findings suggest that, despite a transient increase in pain sensitivity following each treatment, anti-PD-1 immunotherapy could produce long-term benefits in preventing bone destruction and alleviating bone cancer pain by suppressing osteoclastogenesis.
Topics: Animals; Bone Neoplasms; Cancer Pain; Carcinoma, Lewis Lung; Female; Mice; Mice, Knockout; Neoplasm Proteins; Nivolumab; Osteoclasts; Programmed Cell Death 1 Receptor
PubMed: 32484460
DOI: 10.1172/JCI133334