Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance
Katharine A. White1, Bree K. Grillo-Hill2 and Diane L. Barber1,*

 

ABSTRACT

Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH (pHi) and a decreased extracellular pH (pHe) compared with normal cells. Recent work has expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors. Recent findings also show that, by blocking pHi increases, cancer cell behaviors can be attenuated. This suggests ion transporter inhibition as an effective therapeutic approach, either singly or in combination with targeted therapies. In this Cell Science at a Glance article and accompanying poster, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression and adaptation.

The Role of Calcium in Inflammation-Associated Bone Resorption

The Role of Calcium in Inflammation-Associated Bone Resorption
Gordon L. Klein
Department of Orthopaedic Surgery and Rehabilitation, University of Texas Medical Branch and Shriners Burns
Hospital, Galveston, TX 77555-0165, USA; gklein@utmb.edu; Tel.: +1-409-747-5700; Fax: +1-409-770-6919
Received: 28 June 2018; Accepted: 27 July 2018; Published: 1 August 2018

 

Abstract:

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.