PMID- 27429840 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160719 LR - 20240325 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 6 IP - 6 DP - 2016 TI - Defective quorum sensing of acute lymphoblastic leukemic cells: evidence of collective behavior of leukemic populations as semi-autonomous aberrant ecosystems. PG - 1177-230 AB - Quorum sensing (QS) is a generic term used to describe cell-cell communication and collective decision making by bacterial and social insects to regulate the expression of specific genes in controlling cell density and other properties of the populations in response to nutrient supply or changes in the environment. QS mechanisms also have a role in higher organisms in maintaining homeostasis, regulation of the immune system and collective behavior of cancer cell populations. In the present study, we used a p190(BCR-ABL) driven pre-B acute lymphoblastic leukemia (ALL3) cell line derived from the pleural fluid of a terminally ill patient with ALL to test the QS hypothesis in leukemia. ALL3 cells don't grow at low density (LD) in liquid media but grow progressively faster at increasingly high cell densities (HD) in contrast to other established leukemic cell lines that grow well at very low starting cell densities. The ALL3 cells at LD are poised to grow but shortly die without additional stimulation. Supernates of ALL3 cells (HDSN) and some other primary cells grown at HD stimulate the growth of the LD ALL3 cells without which they won't survive. To get further insight into the activation processes we performed microarray analysis of the LD ALL3 cells after stimulation with ALL3 HDSN at days 1, 3, and 6. This screen identified several candidate genes, and we linked them to signaling networks and their functions. We observed that genes involved in lipid, cholesterol, fatty acid metabolism, and B cell activation are most up- or down-regulated upon stimulation of the LD ALL3 cells using HDSN. We also discuss other pathways that are differentially expressed upon stimulation of the LD ALL3 cells. Our findings suggest that the Ph+ ALL population achieves dominance by functioning as a collective aberrant ecosystem subject to defective quorum-sensing regulatory mechanisms. FAU - Patel, Sapan J AU - Patel SJ AD - Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program1275 York Avenue, Box #96, New York, NY 10065, USA; Department of Chemistry and Biomolecular Science, Biochemistry and Proteomics Group, Clarkson University8 Clarkson Avenue, Potsdam, NY 13699-5810, USA. FAU - Dao, Su AU - Dao S AD - Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program 1275 York Avenue, Box #96, New York, NY 10065, USA. FAU - Darie, Costel C AU - Darie CC AD - Department of Chemistry and Biomolecular Science, Biochemistry and Proteomics Group, Clarkson University 8 Clarkson Avenue, Potsdam, NY 13699-5810, USA. FAU - Clarkson, Bayard D AU - Clarkson BD AD - Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program 1275 York Avenue, Box #96, New York, NY 10065, USA. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20160601 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC4937729 OTO - NOTNLM OT - Acute lymphoblastic leukemia OT - FAM129C OT - cancer cell population OT - cancer ecosystem OT - cholesterol metabolism OT - hallmark of cancer OT - quorum sensing EDAT- 2016/07/19 06:00 MHDA- 2016/07/19 06:01 PMCR- 2016/06/01 CRDT- 2016/07/19 06:00 PHST- 2016/03/15 00:00 [received] PHST- 2016/04/04 00:00 [accepted] PHST- 2016/07/19 06:00 [entrez] PHST- 2016/07/19 06:00 [pubmed] PHST- 2016/07/19 06:01 [medline] PHST- 2016/06/01 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2016 Jun 1;6(6):1177-230. eCollection 2016.