Molecular mechanim of cancer-associated bone pain caused by protons

点击翻译按钮获取中文摘要

Bone pain is one of the most common complications associated with bone metastasis. It causes increased morbidity and undermining QOL in cancer patients with bone metastasis. However, the molecular basis of bone pain remains unclear. We reasoned that acidic conditions contribute to bone pain, because cancer creates acidic extracellular microenvironment and acid is a well-known algesic substance.We found that extracellular microenvironment of bone-colonizing cancer was acidic due to proton release via V-ATPase proton pump expressed on plasma membrane. Microarray analysis using primary sensory neuron cells isolated from dorsal root ganglions (DRG) demonstrated that acidic microenvironment increased the transcription of several genes including CGRP and Snap25.Our findings suggest that acidic microenvironments created by cancer cells colonizing bone contribute to elicitation of bone pain through regulating the expression of algogenic genes in DRG sensory neurons.