Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis

Englund, Emelie; Canesin, Giacomo; Papadakos, Konstantinos S.; Vishnu, Neelanjan; Persson, Emma; Reitsma, Bart; Anand, Aseem; Jacobsson, Laila; Helczynski, Leszek; Mulder, Hindrik; Bjartell, Anders; Blom, Anna M.

doi:10.18632/oncotarget.21176

Cited by 49 publications

(74 citation statements)

References 42 publications

(51 reference statements)

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“…Earlier work has suggested that COMP levels in the serum of HCC patients and HCC tissues are abnormally elevated compared with healthy controls and it can be used as diagnostically in the non-invasive estimation of liver cirrhosis and HCC development [ 5 , 6 ]. Recent studies have shown that COMP promotes the progression of breast cancer, colon cancer and prostate cancer [ 7 – 9 ]. These results suggest that COMP may be an important pro-HCC molecule, but the mechanism by which COMP plays a role in HCC still needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

Wang

et al. 2018

J Exp Clin Cancer Res

103

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BackgroundCartilage oligomeric matrix protein (COMP) is known to promote fibrosis in skin, lung and liver. Emerging evidence shows that COMP plays critical roles in tumor development, including breast cancer, colon cancer and hepatocellular carcinoma (HCC). Nevertheless, the role of COMP in HCC proliferation and metastasis and its underlying mechanisms remain fully unclear.MethodsSerum COMP was determined by ELISA. Cell Counting Kit-8 and plate colony formation were performed to evaluate cell proliferation. Wound healing and transwell assays were used to determine migration and invasion of HCC cells. Western blotting and immunofluorescence were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers and MMPs in HCC cells. The in vivo role of COMP was evaluated using mouse models. We also measured effects of hepatic stellate cells (HSCs)-conditioned medium (CM) on HCC progression using transwell coculture system.ResultsHere, we found that serum COMP levels in HCC patients were significantly higher than those in healthy controls. Accordingly, high serum COMP levels in HCC patients significantly correlated with malignant clinical characteristics and poor clinical outcomes. Next, we investigated that recombinant human COMP protein (rCOMP) treatment resulted in increased abilities of proliferation, invasion and migration of HCC cells. Furthermore, rCOMP treatment enhanced proliferative and metastatic colonization of HCC cells in vivo. Mechanistically, CD36 receptor played an essential role in COMP-mediated HCC cell proliferation and metastasis. Functionally, COMP/CD36 signaling caused phosphorylation of ERK and AKT, resulting in the upregulation of tumor-progressive genes such as EMT markers, MMP-2/9, Slug and Twist in HCC cells. Interestingly, we revealed that COMP was secreted by HSCs. CM of LX2 cells with COMP knockdown showed weaker effects on the activation of MEK/ERK and PI3K/AKT signaling pathways in HCC cells compared to control CM.ConclusionsOur findings indicated that HSCs-derived COMP collaborated with CD36 and subsequently played an essential role in MEK/ERK and PI3K/AKT-mediated HCC progression. COMP might act as a promising target for the diagnosis and treatment of aggressive HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0908-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

Wang

et al. 2018

J Exp Clin Cancer Res

103

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“…As a crucial component of ECM, COMP has the capacity to regulate activation of the complement system and thus innate immunity [37]. In addition, high expression of COMP protects the cells from endoplasmic reticulum (ER) stress, and cells overexpressing the COMP gene undergo a metabolic switch known as the Warburg effect [38,39]. Furthermore, high COMP expression plays a crucial role in regulating cellular metabolism by blocking intracellular Ca 2+ signaling and thus blocking the apoptosis process of the cells [39].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, high expression of COMP protects the cells from endoplasmic reticulum (ER) stress, and cells overexpressing the COMP gene undergo a metabolic switch known as the Warburg effect [38,39]. Furthermore, high COMP expression plays a crucial role in regulating cellular metabolism by blocking intracellular Ca 2+ signaling and thus blocking the apoptosis process of the cells [39]. Previous studies have shown that COMP expression in breast cancer cells is significantly associated with poor prognosis [40].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis to Screen the Key Prognostic Genes in Tumor Microenvironment of Bladder Cancer

Zhang

Chen

et al. 2020

BioMed Research International

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Bladder cancer (BLCA) is the fifth most common cancer and has the features of low survival rate and high morbidity and mortality.e Cancer Genome Atlas (TCGA) is a pool of global gene expression profile and contains huge amounts of cancer genomics data, which makes it possible to inquire the relationship between gene expression and prognosis of a series of malignant tumors including BLCA. Immune and stromal cells are two major components of tumor microenvironment (TME) which play an important role in judging the prognosis of tumor and influencing the progression of malignant, inflammatory, and metabolic disorders. In our study, we conducted a quantitative analysis of immune and stromal elements based on the ESTIMATE algorithm and thus divided BLCA cases into high and low groups. en the differentially expressed genes closely related to tumor prognosis between groups were identified and had been shown to correlate with immune response and stromal alterations, which was further confirmed by functional enrichment analysis and protein-protein interaction networks. We validated those genes through BLCA dates downloaded from ArrayExpress and thus got the marker genes to predict prognosis of BLCA. Additionally, immune cell infiltration analysis explored the correlation between the verified genes and immune cells. In conclusion, we identified a series of TME-related genes that assess the prognosis and explored the interaction between TME and tumor prognosis to guide clinical individualized treatment.

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“…Recently, Cartilage Oligomeric Matrix Protein (COMP), which plays an important role in the organization of the extracellular matrix of cartilage, has been identi ed as a potent driver of the progression of prostate cancer, acting in an anti-apoptotic fashion by interfering with the Ca2+ homeostasis of cancer cells [30]. In a retrospective case control series in prostate cancer patients with and without osteoarthritis, this condition was identi ed as an independent risk factor for metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk after total hip replacements. A prospective study of 41,402 patients in the Norwegian Arthroplasty Register linked to the Cancer Registry of Norway

Dybvik

Furnes

Havelin

et al. 2020

Preprint

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Background: Concerns have been raised that implants used in total hip replacements (THR) could lead to increased cancer risk. Several different materials, metals and fixation techniques are used in joint prostheses and different types of articulation can cause an increased invasion of particles or ions into the human body. Methods: Patients with THR registered in the Norwegian Arthroplasty Register during 1987-2009 were linked to the Cancer registry of Norway. Patients with THR due to osteoarthritis, under the age of 75 at time of surgery, were included. Standardized incidence ratios (SIR) were applied to compare cancer risk for THR patients to the general population. Types of THR were divided into cemented (both components), uncemented (both components), and hybrid (cemented femoral and uncemented acetabular components). To account for selection mechanisms, time dependent covariates were applied in Cox-regression, adjusting for cancer risk the first 10 years after surgery. The analyses were adjusted for age, gender and if the patient had additional THR-surgery in the same or the opposite hip. The study follows the STROBE guidelines.Results: Comparing patients with THR to the general population in Norway we found no differences in cancer risk. The overall SIR for the THR-patients after 10 years follow-up was 1.02 (95% CI: 0.97-1.07). For cemented THR, the SIR after 10 years follow-up was 0.99 (95% CI: 0.94-1.05), for uncemented, 1.16 (95% CI: 1.02-1.30), and for hybrid 1.12 (95% CI: 0.91-1.33). Adjusted Cox analyses showed that patients with uncemented THRs had an elevated risk for cancer (hazard ratio: HR=1.24, 95% CI: 1.05-1.46, p=0.009) when compared to patients with cemented THRs after 10 years follow-up. Stratified by gender the increased risk was only present for men. The risk for patients with hybrid THRs was not significantly increased (HR=1.07, 95% CI: 0.85-1.35, p=0.55) compared to patients with cemented THRs.Conclusions: THR patients had no increased risk for cancer compared to the general population. We found, however, that receiving an uncemented THR was associated with a small increased risk for cancer compared to cemented THR in males, but that this may be prone to unmeasured confounding.

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Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis

Cited by 49 publications

References 42 publications

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways

Bioinformatics Analysis to Screen the Key Prognostic Genes in Tumor Microenvironment of Bladder Cancer

Cancer risk after total hip replacements. A prospective study of 41,402 patients in the Norwegian Arthroplasty Register linked to the Cancer Registry of Norway

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