High Levels of Expression of Cartilage Oligomeric Matrix Protein in Lymph Node Metastases in Breast Cancer Are Associated with Reduced Survival

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Dec 10

PMID 34884987

Citations 6

Authors

Konstantinos S Papadakos

Catharina Hagerling

Lisa Ryden

Anna-Maria Larsson

Anna M Blom

Affiliations

Soon will be listed here.

Abstract

Cartilage oligomeric matrix protein (COMP) is a regulator of the extracellular matrix and is expressed primarily in the cartilage. Recently, COMP expression was also documented in breast cancer patients both in sera and tumor biopsies, in both of which it could serve as an independent prognostic marker. This study aimed to assess COMP as a potential biomarker in the group of metastatic breast cancer patients. Levels of COMP were measured by ELISA in serum samples of 141 metastatic breast cancer patients. Biopsies from primary tumors, synchronous lymph node metastases, and distant metastases were stained for COMP expression. The levels of serum COMP were higher in patients with ER- and HER2-positive tumors when compared to triple-negative tumors and correlated with the presence of bone and lung metastases, circulating tumor cell count, and clusters. Most of the primary tumors expressing COMP (70%) retained the expression also in the lymph node metastases, which correlated with visceral metastases and reduced survival. In conclusion, COMP appears as a valuable biomarker in metastatic breast cancer patients indicating a more severe stage of the disease. Serum COMP levels were associated with specific types of metastases in patients with metastatic breast cancer emphasizing that further studies are warranted to elucidate its potential role as a monitoring marker.

Citing Articles

Intracellular cartilage oligomeric matrix protein augments breast cancer resistance to chemotherapy.

Hanitrarimalala V, Bednarska I, Murakami T, Papadakos K, Blom A Cell Death Dis. 2024; 15(7):480.

PMID: 38965233 PMC: 11224260. DOI: 10.1038/s41419-024-06872-7.

Cartilage Oligomeric Matrix Protein in Osteoarthritis and Obesity-Do New Considerations Emerge?.

Lambova S, Batsalova T, Moten D, Dzhambazov B Int J Mol Sci. 2024; 25(10).

PMID: 38791302 PMC: 11121003. DOI: 10.3390/ijms25105263.

PEOPLE (NTC03447678), a phase II trial to test pembrolizumab as first-line treatment in patients with advanced NSCLC with PD-L1 <50%: a multiomics analysis.

Lo Russo G, Prelaj A, Dolezal J, Beninato T, Agnelli L, Triulzi T J Immunother Cancer. 2023; 11(6).

PMID: 37286305 PMC: 10254948. DOI: 10.1136/jitc-2023-006833.

Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma.

Lapitz A, Azkargorta M, Milkiewicz P, Olaizola P, Zhuravleva E, Grimsrud M J Hepatol. 2023; 79(1):93-108.

PMID: 36868481 PMC: 10292605. DOI: 10.1016/j.jhep.2023.02.027.

Transformer for Gene Expression Modeling (T-GEM): An Interpretable Deep Learning Model for Gene Expression-Based Phenotype Predictions.

Zhang T, Hasib M, Chiu Y, Han Z, Jin Y, Flores M Cancers (Basel). 2022; 14(19).

PMID: 36230685 PMC: 9562172. DOI: 10.3390/cancers14194763.

References

Mundermann A, Dyrby C, Andriacchi T, King K . Serum concentration of cartilage oligomeric matrix protein (COMP) is sensitive to physiological cyclic loading in healthy adults. Osteoarthritis Cartilage. 2005; 13(1):34-8. DOI: 10.1016/j.joca.2004.09.007. View

Tian C, Ohlund D, Rickelt S, Lidstrom T, Huang Y, Hao L . Cancer Cell-Derived Matrisome Proteins Promote Metastasis in Pancreatic Ductal Adenocarcinoma. Cancer Res. 2020; 80(7):1461-1474. PMC: 7127978. DOI: 10.1158/0008-5472.CAN-19-2578. View

Liang Y, Fu Y, Qi R, Wang M, Yang N, He L . Cartilage oligomeric matrix protein is a natural inhibitor of thrombin. Blood. 2015; 126(7):905-14. DOI: 10.1182/blood-2015-01-621292. View

Forslind K, Eberhardt K, Jonsson A, Saxne T . Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis. Br J Rheumatol. 1992; 31(9):593-8. DOI: 10.1093/rheumatology/31.9.593. View

DiCesare P, Hauser N, Lehman D, Pasumarti S, Paulsson M . Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett. 1994; 354(2):237-40. DOI: 10.1016/0014-5793(94)01134-6. View

Happonen K, Saxne T, Geborek P, Andersson M, Bengtsson A, Hesselstrand R . Serum COMP-C3b complexes in rheumatic diseases and relation to anti-TNF-α treatment. Arthritis Res Ther. 2012; 14(1):R15. PMC: 3392805. DOI: 10.1186/ar3694. View

Englund E, Canesin G, Papadakos K, Vishnu N, Persson E, Reitsma B . Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis. Oncotarget. 2017; 8(58):98298-98311. PMC: 5716730. DOI: 10.18632/oncotarget.21176. View

Saxne T, Heinegard D . Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992; 31(9):583-91. DOI: 10.1093/rheumatology/31.9.583. View

Li Q, Wang C, Wang Y, Sun L, Liu Z, Wang L . HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways. J Exp Clin Cancer Res. 2018; 37(1):231. PMC: 6146743. DOI: 10.1186/s13046-018-0908-y. View

10.

Posey K, Coustry F, Hecht J . Cartilage oligomeric matrix protein: COMPopathies and beyond. Matrix Biol. 2018; 71-72:161-173. PMC: 6129439. DOI: 10.1016/j.matbio.2018.02.023. View

11.

Papadakos K, Bartoschek M, Rodriguez C, Gialeli C, Jin S, Lendahl U . Cartilage Oligomeric Matrix Protein initiates cancer stem cells through activation of Jagged1-Notch3 signaling. Matrix Biol. 2018; 81:107-121. DOI: 10.1016/j.matbio.2018.11.007. View

12.

Larsson A, Jansson S, Bendahl P, Jorgensen C, Loman N, Graffman C . Longitudinal enumeration and cluster evaluation of circulating tumor cells improve prognostication for patients with newly diagnosed metastatic breast cancer in a prospective observational trial. Breast Cancer Res. 2018; 20(1):48. PMC: 5994056. DOI: 10.1186/s13058-018-0976-0. View

13.

Aceto N, Bardia A, Miyamoto D, Donaldson M, Wittner B, Spencer J . Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014; 158(5):1110-1122. PMC: 4149753. DOI: 10.1016/j.cell.2014.07.013. View

14.

Rizwan A, Bulte C, Kalaichelvan A, Cheng M, Krishnamachary B, Bhujwalla Z . Metastatic breast cancer cells in lymph nodes increase nodal collagen density. Sci Rep. 2015; 5:10002. PMC: 4423440. DOI: 10.1038/srep10002. View

15.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

16.

Hultman K, Edsfeldt A, Bjorkbacka H, Duner P, Sundius L, Nitulescu M . Cartilage Oligomeric Matrix Protein Associates With a Vulnerable Plaque Phenotype in Human Atherosclerotic Plaques. Stroke. 2019; 50(11):3289-3292. DOI: 10.1161/STROKEAHA.119.026457. View

17.

Wang L, Wang X, Kong W . ADAMTS-7, a novel proteolytic culprit in vascular remodeling. Sheng Li Xue Bao. 2010; 62(4):285-94. View

18.

Papadakos K, Darlix A, Jacot W, Blom A . High Levels of Cartilage Oligomeric Matrix Protein in the Serum of Breast Cancer Patients Can Serve as an Independent Prognostic Marker. Front Oncol. 2019; 9:1141. PMC: 6831625. DOI: 10.3389/fonc.2019.01141. View

19.

Englund E, Bartoschek M, Reitsma B, Jacobsson L, Escudero-Esparza A, Orimo A . Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer. Oncogene. 2016; 35(43):5585-5596. DOI: 10.1038/onc.2016.98. View

20.

Riessen R, Fenchel M, Chen H, Axel D, Karsch K, Lawler J . Cartilage oligomeric matrix protein (thrombospondin-5) is expressed by human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2001; 21(1):47-54. DOI: 10.1161/01.atv.21.1.47. View