To identify variables having a critical role in prostate cancer patients experiencing osteo-metastasis.
Prostatic carcinoma is a multifactorial complex disorder that exhibits increased propensity to develop bone metastasis. An interplay of inflammatory and bone remodelling parameters promotes formation of pre-metastatic niches in bones of patients, which could render them more vulnerable to skeletal disabilities.
To evaluate the multi-dynamic inter-relationship of circulating variables in prostate cancer patients experiencing osteometastasis.
Fifty-seven (n=57) men with clinically confirmed prostate cancer, fifty-nine (n=59) with skeletal metastases and one hundred (n=100) healthy subjects i.e., men aging from 53-84 years with no clinical evidence of prostate were recruited from the Jinnah Hospital Lahore, Pakistan. Informed consent was obtained, and a venous blood sample was drawn and stored at -70 oC until assayed. Levels of variables were evaluated using appropriate methods. Levels of matrix metalloproteinases (MMPs), osteopontin (OPN), TGH-β, and sRANKL were estimated by the ELISA method. Each sample was suspended and the given protocol was employed. ELISA readings were obtained for the estimation of all variables.
Highly significant (P ˂ 0.05) differential expression of oxidative stress, inflammatory cytokines and bone remodelling variables was observed in localized and osteo-metastatic CA prostate patients. A strong positive correlation was revealed among OPN, sRANKL, MMP-7, MMP-9, PSA and TGF-β (OPN vs MMP-7, r=0.698* and OPN vs MMP-9, r=0.765**, OPN vs RANKL, =0.856*, sRANKL vs MMP-9, r=0.825**, TGF-β vs RANKL, r=0.868* and PSA vs TGF- β, r=0.752*); lower levels of OPG were estimated in metastasized patients, showing that both osteolytic and osteoblastic phases of bone remodelling occur simultaneously.
The altered oxidative and inflammatory responses endorse matrix metalloproteinases (MMPs) increased activity, RANKL/OPG imbalance and enhanced bone matrix proteins turnover, which can foster the process of osteo-metastasis. The perturbed RANKL/OPG drift and enhanced PSA levels are associated with increased TGF-β activity to aggravate epithelial mesenchymal transition (EM) and osteo-tropism of prostate cancer. Thus, designing novel targets of these major variables can minimize the incidence of prostate cancer patients.
Anti-cancer agents in medicinal chemistry. 2020 Jul 26 [Epub ahead of print]
Muhammad Abdul Basit Ashraf, Ayesha Zahid, Shazia Ashraf, Sulayman Waquar, Saima Iqbal, Arif Malik
Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore. Pakistan., Department of Pathology, Independent Medical College, Faisalabad. Pakistan.