PMID- 27141354
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 5
IP  - 3
DP  - 2016 Mar
TI  - Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.
PG  - e1093277
LID - e1093277
AB  - Tumor-associated macrophages (TAMs) play an important role in tumor progression, 
      suppression of antitumor immunity and dissemination. Blood monocytes infiltrate 
      the tumor region and are primed by local microenvironmental conditions to promote 
      tumor growth and invasion. Although many of the interacting cytokines and factors 
      are known for the tumor-macrophage interactions, the putative contribution of 
      circulating tumor cells (CTCs) is not known so far. These specialized cells are 
      characterized by increased mobility, ability to degrade the extracellular matrix 
      (ECM) and to enter the blood stream and generate secondary lesions which is a 
      leading cause of death for the majority of tumor patients. The first 
      establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples 
      of advanced stage small cell lung cancer (SCLC) patients allowed us to 
      investigate the CTC-immune cell interaction. Cocultures of peripheral blood 
      mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium 
      (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance 
      of CD14(+), CD163(weak) and CD68(+) macrophages expressing markers of TAMs. 
      Furthermore, we screened the supernatants of CTC-primed macrophages for presence 
      of approximately 100 cytokines and compared the expression with those induced by 
      the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM 
      showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 
      (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and 
      matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In 
      contrast, BHGc7-CM induced marked overexpression of complement factor D 
      (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, 
      lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived 
      independently from relapsed SCLC, revealed an almost identical pattern with added 
      expression of ENA-78/CXCL5. CMs of the non-tumor HEK293 cell line revealed no 
      induction of macrophages, whereas incubation of PBMNCs with recombinant CHI3L1 
      gave positive results. Thus, the specific contributions of CTCs in SCLC affect 
      CFD/adipsin, possibly involved in immunity/cachexia, VDBP which gives rise to 
      group-specific component protein-derived macrophage-activating factor (GcMAF), 
      GDF-15/MIC-1 which enhances the malignant phenotype of tumor cells and 
      ENA-78/CXCL5 which attracts angiogenic neutrophils. In conclusion, CTCs are 
      competent to specifically manipulate TAMs to increase invasiveness, angiogenesis, 
      immunosuppression and possibly lipid catabolism.
FAU - Hamilton, Gerhard
AU  - Hamilton G
AD  - Department of Surgery, Medical University Vienna , Vienna, Austria.
FAU - Rath, Barbara
AU  - Rath B
AD  - Ludwig Boltzmann Cluster of Translational Oncology , Vienna, Austria.
FAU - Klameth, Lukas
AU  - Klameth L
AD  - Ludwig Boltzmann Cluster of Translational Oncology , Vienna, Austria.
FAU - Hochmair, Maximilan J
AU  - Hochmair MJ
AD  - Respiratory Oncology Unit, Otto Wagner Hospital , Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20151029
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC4839345
OTO - NOTNLM
OT  - Cachexia
OT  - circulating tumor cells
OT  - cytokines
OT  - small cell lung cancer
OT  - tumor-associated macrophages
EDAT- 2016/05/04 06:00
MHDA- 2016/05/04 06:01
PMCR- 2016/10/29
CRDT- 2016/05/04 06:00
PHST- 2015/05/20 00:00 [received]
PHST- 2015/08/25 00:00 [revised]
PHST- 2015/09/04 00:00 [accepted]
PHST- 2016/05/04 06:00 [entrez]
PHST- 2016/05/04 06:00 [pubmed]
PHST- 2016/05/04 06:01 [medline]
PHST- 2016/10/29 00:00 [pmc-release]
AID - 1093277 [pii]
AID - 10.1080/2162402X.2015.1093277 [doi]
PST - epublish
SO  - Oncoimmunology. 2015 Oct 29;5(3):e1093277. doi: 10.1080/2162402X.2015.1093277. 
      eCollection 2016 Mar.