Differentiation between Cancerous and Normal Hyperplastic Lobules in Breast Lesions

The directional movement of cells can be regulated by ATP, certain other nucleotides (e.g., ADP, UTP), and adenosine. Such regulation occurs for cells that are "professional phagocytes" (e.g., neutrophils, macrophages, certain lymphocytes, and microglia) and that undergo directional migration and subsequent phagocytosis. Numerous other cell types (e.g., fibroblasts, endothelial cells, neurons, and keratinocytes) also change motility and migration in response to ATP, other nucleotides, and adenosine. In this article, we review how nucleotides and adenosine modulate chemotaxis and motility and highlight the importance of nucleotide-and adenosine-regulated cell migration in several cell types: neutrophils, microglia, endothelial cells, and cancer cells. We also discuss difficulties in conducting experiments and drawing conclusions regarding the ability of nucleotides and adenosine to modulate the migration of professional and non-professional phagocytes.

Section: Cancer Cellsmentioning

confidence: 99%

New insights regarding the regulation of chemotaxis by nucleotides, adenosine, and their receptors

Corriden

Insel

2012

“…So far, no extensive screening of P2X 7 expression in malignant tumours has been performed; however, different laboratories have reported increased expression of this receptor in prostate [30], breast and skin cancers [31,32], neuroblastoma [9], leukemia [6] and thyroid papillary carcinoma [33]. In most cases, these studies simply report histological evidence of receptor overexpression in tissue slices, with no analysis of functional activity.…”

Section: P2x 7 and Cancermentioning

confidence: 99%

P2X7: a growth-promoting receptor—implications for cancer

Virgilio

Ferrari

Adinolfi

2009

129

114

The P2X 7 receptor is widely referred to as the paradigmatic cytotoxic nucleotide receptor, and is often taken as an epitome of cytotoxic receptors as a whole. However, cytotoxicity is the result of sustained pharmacological stimulation, which is likely to occur in vivo only under severe pathological conditions. Over the years, we have gathered robust experimental proof that led us to adopt an entirely different view, pointing to P2X 7 as a survival/growth-promoting rather than death-inducing receptor. Evidence in favour of this role is manifold: (1) extracellular ATP and benzoyl ATP support cell proliferation in peripheral T lymphocytes via a P2X 7 -like receptor; (2) P2X 7 transfection into several cell lines confers growth advantage; (3) HEK293 cells transfected with P2X 7 show enhanced mitochondrial metabolic activity and growth; (4) lipopolysaccharide (LPS)-dependent growth arrest of microglia is mediated via P2X 7 down-modulation; (5) several malignant tumours express high P2X 7 levels and (6) the ATP concentration in tumour interstitium is severalfold higher than in healthy tissues, to a level in principle sufficient to activate the P2X 7 receptor. The molecular basis of P2X 7 -mediated growth-promoting activity is poorly known, but mitochondria appear to play a central role. A deeper understanding of the role played by P2X 7 in cell proliferation might provide an insight into the mechanism of normal and malignant cell growth and suggest novel anti-tumour therapies.

“…P2 receptors are also expressed in many types of cancer [9]. Among these molecules, P2X7 receptor shows increased expression in many types of cancer cells [10][11][12][13][14]. Furthermore, activation of P2X7 receptor has been implicated in tumor growth, as well as tumor angiogenesis and metastasis of breast cancer [6, 10-12, 15, 16].…”

Section: Introductionmentioning

confidence: 99%

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Takai

Tsukimoto

Hishida

et al. 2014

Extracellular nucleotides, such as ATP, are released from cells and play roles in various physiological and pathological processes through activation of P2 receptors. Here, we show that autocrine signaling through release of ATP and activation of P2X7 receptor influences migration of human lung cancer cells. Release of ATP was induced by stimulation with TGF-β1, which is a potent inducer of cell migration, in human lung cancer H292 cells, but not in noncancerous BEAS-2B cells. Treatment of H292 cells with a specific antagonist of P2X7 receptor resulted in suppression of TGF-β1-induced migration. PC-9 human lung cancer cells released a large amount of ATP under standard cell culture conditions, and P2X7 receptor-dependent dye uptake was observed even in the absence of exogenous ligand, suggesting constitutive activation of P2X7 receptor in this cell line. PC-9 cells showed high motile activity, which was inhibited by treatment with ecto-nucleotidase and P2X7 receptor antagonists, whereas a P2X7 receptor agonist enhanced migration. PC-9 cells also harbor a constitutively active mutation in epidermal growth factor receptor (EGFR). Treatment with EGFR tyrosine kinase inhibitor AG1478 suppressed both cell migration and P2X7 receptor expression in PC-9 cells. Compared to control PC-9 cells, cells treated with P2X7 antagonist exhibited broadened lamellipodia around the cell periphery, while AG1478-treated cells lacked lamellipodia. These results indicate that P2X7-mediated signaling and EGFR signaling may regulate migration of PC-9 cells through distinct mechanisms. We propose that autocrine ATP-P2X7 signaling is involved in migration of human lung cancer cells through regulation of actin cytoskeleton rearrangement.