Endothelial cell Ca2+ increases upon tumor cell contact and modulates cell-cell adhesion

Area of Science:

• Cell Biology
• Cancer Research
• Biochemistry

Background:

• Mechanisms of tumor cell adhesion to endothelial cells are not fully understood.
• Endothelial cell calcium signaling plays a role in cell-cell interactions.

Purpose of the Study:

• To investigate the effect of tumor cell contact on endothelial cell calcium levels.
• To determine the role of calcium signaling in tumor cell-endothelial cell adhesion.

Main Methods:

• Indo-1 loaded bovine artery endothelial cells were used to measure cytosolic calcium ([Ca2+]).
• Tumor cells (murine melanoma, human prostate carcinoma), neutrophils, lymphoma cells, red blood cells, and inert beads were used for cell contact studies.
• Thapsigargin and a calcium chelator (BAPTA) were used to investigate calcium stores and signaling pathways.
• Cell adhesion was assessed under static and dynamic flow conditions.

Main Results:

• Tumor cell contact caused a rapid increase in endothelial cell [Ca2+], unlike contact with inert beads or non-tumor cells.
• The calcium increase was independent of extracellular calcium but was abolished by thapsigargin, indicating release from intracellular stores.
• Pretreatment with a calcium chelator inhibited both the [Ca2+] rise and melanoma cell adhesion to endothelial cells.

Conclusions:

• Tumor cell contact induces a rapid release of Ca2+ from endothelial cell intracellular stores.
• This calcium signaling is essential for enhancing tumor cell adhesion to endothelial cells.
• Understanding this mechanism could reveal new therapeutic targets for cancer metastasis.