Leptin, Leptin Receptor, KHDRBS1 (KH RNA Binding Domain Containing, Signal Transduction Associated 1), and Adiponectin in Bone Metastasis from Breast Carcinoma: An Immunohistochemical Study.

Paola Maroni,Luca Cannavò,Alessandro Luzzati,Paola Bendinelli,Giuseppe Perrucchini

doi:10.3390/biomedicines8110510

Abstract

Breast cancer patients are at a high risk of complications from bone metastasis. Molecular characterization of bone metastases is essential for the discovery of new therapeutic targets. Here, we investigated the expression and the intracellular distribution of KH RNA binding domain containing, signal transduction associated 1 (KHDRBS1), leptin, leptin receptor (LEPR), and adiponectin in bone metastasis from breast carcinoma and looked for correlations between the data. The expression of these proteins is known in breast carcinoma, but it has not been investigated in bone metastatic tissue to date. Immunohistochemical analysis was carried out on bone metastasis specimens, then semiquantitative evaluation of the results and the Pearson test were performed to determine eventual correlations. KHDRBS1 expression was significantly higher in the nuclei than in the cytosol of metastatic cells; LEPR was prevalently observed in the cytosol and the nuclei; leptin and adiponectin were found in metastatic cells and stromal cells; the strongest positive correlation was between nuclear KHDRBS1 and nuclear LEPR expression. Taken together, our findings support the importance of the leptin/LEPR/KHDRBS1 axis and of adiponectin in the progression of bone metastasis and suggest their potential application in pharmacological interventions.

Highlights

IntroductionBreast cancer is the second leading cause of death among women worldwide [1]
Breast cancer is the second leading cause of death among women worldwide [1]. mortality rates have declined, the incidence after menopause continues to rise
We investigated the expression and the intracellular distribution of KHDRBS1, leptin, and leptin receptor (LEPR) in bone metastasis from breast carcinoma and looked for eventual correlations between them

Summary

Introduction

Breast cancer is the second leading cause of death among women worldwide [1]. Mortality rates have declined, the incidence after menopause continues to rise. Therapeutic failure is largely due to the heterogeneity of breast cancer subtypes and clinical features, as well as the spread and development of secondary growth in bone and lung and associated complications [2]. Bone metastases often occur in breast cancer [3]. Bone is a special organ: mineral content, matrix. Biomedicines 2020, 8, 510 composition, extreme rigidity, highly hypoxic environment, acidic pH, and high concentrations of extracellular calcium create a fertile ground for neoplastic cells to grow. The hallmarks of bone metastases are skeletal fractures, nerve compression, and pain—so-called skeletal-related events (SREs)—that worsen the quality of life and compromise survival [4]

Results

Discussion

Conclusion