PMID- 31533245
OWN - NLM
STAT- MEDLINE
DCOM- 20200204
LR  - 20200204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 18
DP  - 2019 Sep 17
TI  - Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune 
      Evasion.
LID - 10.3390/ijms20184588 [doi]
LID - 4588
AB  - Extracellular heat shock proteins (ex-HSPs) have been found in exosomes, 
      oncosomes, membrane surfaces, as well as free HSP in cancer and various 
      pathological conditions, also known as alarmins. Such ex-HSPs include HSP90 (alpha, 
      beta, Gp96, Trap1), HSP70, and large and small HSPs. Production of HSPs is 
      coordinately induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 
      (HIF-1), while matrix metalloproteinase 3 (MMP-3) and heterochromatin protein 1 
      are novel inducers of HSPs. Oncosomes released by tumor cells are a major aspect 
      of the resistance-associated secretory phenotype (RASP) by which immune evasion 
      can be established. The concepts of RASP are: (i) releases of ex-HSP and HSP-rich 
      oncosomes are essential in RASP, by which molecular co-transfer of HSPs with 
      oncogenic factors to recipient cells can promote cancer progression and 
      resistance against stresses such as hypoxia, radiation, drugs, and immune 
      systems; (ii) RASP of tumor cells can eject anticancer drugs, targeted 
      therapeutics, and immune checkpoint inhibitors with oncosomes; (iii) cytotoxic 
      lipids can be also released from tumor cells as RASP. ex-HSP and membrane-surface 
      HSP (mHSP) play immunostimulatory roles recognized by CD91+ scavenger receptor 
      expressed by endothelial cells-1 (SREC-1)+ Toll-like receptors (TLRs)+ 
      antigen-presenting cells, leading to antigen cross-presentation and T cell 
      cross-priming, as well as by CD94+ natural killer cells, leading to tumor 
      cytolysis. On the other hand, ex-HSP/CD91 signaling in cancer cells promotes 
      cancer progression. HSPs in body fluids are potential biomarkers detectable by 
      liquid biopsies in cancers and tissue-damaged diseases. HSP-based vaccines, 
      inhibitors, and RNAi therapeutics are also reviewed.
FAU - Taha, Eman A
AU  - Taha EA
AD  - Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan. 
      pj7l8pfb@s.okayama-u.ac.jp.
AD  - Department of Medical Bioengineering, Graduate School of Natural Science and 
      Technology, Okayama University, Okayama 700-8530, Japan. 
      pj7l8pfb@s.okayama-u.ac.jp.
AD  - Department of Biochemistry, Ain Shams University Faculty of Science, Cairo 11566, 
      Egypt. pj7l8pfb@s.okayama-u.ac.jp.
FAU - Ono, Kisho
AU  - Ono K
AD  - Department of Oral and Maxillofacial Surgery, Okayama University Hospital, 
      Okayama 700-0914, Japan. de20012@s.okayama-u.ac.jp.
FAU - Eguchi, Takanori
AU  - Eguchi T
AUID- ORCID: 0000-0002-3297-6126
AD  - Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan. 
      eguchi.takanori@gmail.com.
AD  - Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of 
      Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 
      700-8525, Japan. eguchi.takanori@gmail.com.
LA  - eng
GR  - 17K11642/Japan Society for the Promotion of Science/
GR  - 18K09789/Japan Society for the Promotion of Science/
GR  - 17K11669/Japan Society for the Promotion of Science/
PT  - Journal Article
PT  - Review
DEP - 20190917
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Extracellular Space/*metabolism
MH  - Extracellular Vesicles/metabolism
MH  - Heat-Shock Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Humans
MH  - *Immune Evasion/genetics
MH  - Immune System/immunology/metabolism
MH  - *Immunologic Surveillance/genetics
MH  - Immunomodulation
MH  - Liquid Biopsy
MH  - Molecular Targeted Therapy
MH  - Neoplasms/drug therapy/etiology/metabolism/pathology
MH  - Receptors, Cell Surface/metabolism
PMC - PMC6770223
OTO - NOTNLM
OT  - alarmin
OT  - biomarker
OT  - exosome
OT  - heat shock protein (HSP)
OT  - hypoxia
OT  - immune evasion
OT  - immune surveillance
OT  - immunology
OT  - oncosome
OT  - resistance-associated secretory phenotype (RASP)
COIS- The authors declare no conflict of interest.
EDAT- 2019/09/20 06:00
MHDA- 2020/02/06 06:00
PMCR- 2019/09/01
CRDT- 2019/09/20 06:00
PHST- 2019/08/16 00:00 [received]
PHST- 2019/09/13 00:00 [revised]
PHST- 2019/09/14 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/09/01 00:00 [pmc-release]
AID - ijms20184588 [pii]
AID - ijms-20-04588 [pii]
AID - 10.3390/ijms20184588 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Sep 17;20(18):4588. doi: 10.3390/ijms20184588.