Table 2.

Expression and process regulated by of purinergic elements in the most lethal cancers from the reproductive system

Purinergic element	Effect	Model	Reference
Breast carcinoma
P2X7R	Hypoxia promotes P2X7R over expression and activity of this receptor induces an invasive phenotype.	MDA-MB-231 MCF-7	[35]
P2X7R	The receptor is over expressed, its activation increments cell migration and invasion and induces EMT markers.	T47D	[36]
P2X7R	Loss of function mutation (E496A) in host, induces fail in chemotherapy with anthracyclins	Tumors from xenotransplanted EL4 lymphoma cells in P2X7−/− mouse	[37]
P2X7R and P2Y11R	Reduction of vascular endothelial permeability	Tumor vascular endothelial cells associated to breast cancer (BTEC)	[38]
P2Y2R	Favors the formation of the pre-metastatic niche and supports metastasis	MDA-MB-231 cells xenotransplanted in nude mice.	[39]
P2Y2R	Modulation of estrogen-induced proliferation and induction of cell migration.	MCF-7 cells	[40, 41]
P2Y2R	Induction of cell proliferation, migration, invasion and EMT.	MDA-MB-231 cells	[40–43]
P2Y2R	This receptor increments the expression of the NLRC4 inflammasome components as well as IL-1β in response to radiotherapy.	Radiotherapy resistant or normal MDA-MB-231 cells	[44]
P2Y6R	The receptor is over expressed and its activity favors metastasis induction	Tumor biopsies MDA-MB-231 cells xenotransplanted in nude mice.	[45]
P2Y12R	The receptor facilitates the interaction between platelets and breast cancer cells, contributing to metastasis	MCF-7, MDA-MB-468, MDA-MB-231	[46]
AdoR1	Induction of cell proliferation and inhibition of apoptosis	MDA-MB-438 MCF-7	[47, 48]
CD73	Production of ADO by this enzyme repress maturation and cytotoxic actions of NK cells	4T1.2 breast cells xenotrasplanted in mice	[49, 50]
CD73	Favors EMT and induce metastasis	MDA-MB-231 and 4T1	[51]
AdoR2B	Stimulation of cell proliferation, migration and metastases	MDA-MB-231	[52, 53]
AdoR2B	Antagonism of this receptor inhibits CSC selection; furthermore, in previously selected CSC antagonists induce cell death.	Selection of CSC by sphere formation from MDA-MB-231 or MCF-7 cells	[54]
AdoR2B	Its activity favors the enrichment of cultures with cells expressing CSC markers	Selection of CSC by hypoxia in MCF-7, MDA-MB-231 and SUM-149 lines.	[55]
AdoR3	Receptor over expression in tumor tissue	Carcinoma biopsies	[56]
AdoR3	Induce the reduction of cell proliferation and migration	MCF-7 and MDA-MB-231	[57, 58]
AdoR3	Promotes bone metastasis	MRMT-1 cells injected in tibia of rats	[59]
AdoR3	Its pharmacological activation inhibits CSC selection to form mammospheres	MCF-7 and MDA-MB-231	[60]
CD73	Its overexpression leads to immune evasion and is correlated with the induction of other immune check point proteins such as PDL1.	Murine triple negative breast cancer	[61]
CD73	Neutralizing antibodies against this enzyme enhance the effect of chemotherapy and inhibit cell migration, invasion and autophagy. In vivo inhibits lung metastasis and enhances the effect of trastuzumab, a Her2 neutralizing antibody.	MDA-MB-231 and MDA-MB-468. Her2+ breast cancer	[62, 63]
Prostate
P2X5R	Its activity inhibits of cell growth and induces apoptosis	PC3 and DU145 cells	[64]
P2X7R	It is overexpressed in biopsies of PCa but is not detectable in non-cancerous tissue	Human biopsies	[65]
P2X7R	It is highly expressed, its activation induce increment in [Ca2+]i, invasiveness and EMT. Also favors metastases to lymphatic nodes and kidney.	1E8 (highly metastatic) and 2B4 (non-metastatic) clones derived from PC3 line in vitro or xenotransplanted in nude mice.	[66]
P2X7R	A variant lacking “megapore” formation function named nfP2X7R is expressed. Its deletion promotes apoptosis.	PC3, DU145, and LNCaP lines	[67]
P2Y11	Its function inhibits cell proliferation	PC3 and DU145 cells	[68]
P2Y1	Its activation with MRS2365 and new ligands on based on 1-indolinoalkyl 2-phenolic inhibits cell proliferation and induce apoptosis.	PC3 and DU145 cells	[69, 70]
P2Y2R	Its activity promotes cell migration and EMT	1E8 (highly metastatic) and 2B4 (non-metastatic) clones derived from PC3 line, through transactivation of EGFR	[71, 72]
AdoR3	Its activity induce apoptosis	PC3, DU145 and LNCaP cells	[73]
AdoR2B	This receptor promotes proliferation and inhibition of apoptosis	PC3 cells	[74]
Cervix
P2X7R	Its function induces apoptosis	CaSki cells	[75]
P2X7JR	This variant of P2X7R lacks the second transmembrane, showing a dominant negative effect on channel function, inhibiting apoptosis induction by wt receptor	CaSki cells	[76, 77]
P2X7R	It is well expressed in normal tissue but downregulated in cancerous tissue, this downregulation prevents activation of apoptosis	Human biopsies (42 normal and 47 cancerous)	[78]
P2Y1R	Promotes proliferation transactivating EGFR through a pathway that involves PKC, Src and cell surface metalloproteases	HeLa cells	[167
P2Y2R	Its activation induced Ca2+ mobilization, c-Fos expression, ERK phosphorylation and cell proliferation. Also regulates Na+/K+-ATPase activity.	HeLa cells	[79–81]
P2Y6R	Induce Ca2+ mobilization, activation of conventional and atypical PKC’s and cell proliferation	HeLa cells	[82]
Ovarian carcinoma
P2X7R	Is over expressed in cancerous tissue from different carcinoma types. Its activity supports cell proliferation and viability.	Human biopsies SKOV-3 and CAOV-3 cells	[83, 84]
P2Y2R	Its activity induces intracellular Ca2+ mobilization and down regulation of cell proliferation	EFO-21, EFO-27,	[85]
P2Y2R	Its activity induces intracellular Ca2+ mobilization and favors cell proliferation	IOSE29 (preneoplasic) and IOSE29EC (neoplasic)cells	[86]
P2Y2R	Induces increment of cell migration and EMT	SKOV-3 cells	[87]
AdoR2B AdoR3	Its stimulation reduces cell viability and activates apoptosis	CAOV-4 and OVCAR-3 cells	[88, 89]
CD73	Through a meta-analysis it was proposed as a poor prognosis factor	High degree serous carcinoma (more than 1500 patients)	[90, 91]
CD39 and CD73	Both contribute to immune evasion of the tumor	Intratumor stromal cells from biopsies.	[92]
CD39 and CD73	Attraction of myeloid cells to be differentiated in TAM.	Skov-3 cells	[93]