Aims:
To identify variables having a critical role in prostate cancer patients experiencing osteometastasis.
Background:
Prostatic carcinoma is a multifactorial complex disorder that exhibits an increased propensity to
develop bone metastasis. An interplay of inflammatory and bone remodeling parameters promotes the formation
of pre-metastatic niches in bones of patients, which could render them more vulnerable to skeletal disabilities.
Objective:
To evaluate the multi-dynamic inter-relationship of circulating variables in prostate cancer patients
experiencing osteo-metastasis.
Materials and Methods:
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 -70oC 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.
Conclusion:
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.
Results:
Highly significant (P˂0.05) differential expression of oxidative stress, inflammatory cytokines, and
bone remodeling variables were 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 remodeling occur simultaneously.
Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH
