Linked Life Data

19879425

Source:http://linkedlifedata.com/resource/pubmed/id/19879425

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-11-2
pubmed:abstractText
Cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. The microenvironment can exert profound epigenetic effects on cells through cell-derived interactions between cells, or through cell-derived factors deposited into the microenvironment. Tumor progression implies immune-escaping and triggers several processes that synergistically induce a cooperation among transformed and stromal cells, that compete for space and resources such as oxygen and nutrients. Therefore, the extra cellular milieu and tissue microenvironment heterotypic interactions cooperate to promote tumor growth, angiogenesis, and cancer cell motility, through elevated secretion of pleiotropic cytokines and soluble factors. Clusterin (CLU), widely viewed as an enigmatic protein represents one of the numerous cellular factors sharing the intracellular information with the microenvironment and it has also a systemic diffusion, tightly joining the "In and the Out" of the cell with a still debated variety of antagonistic functions. The multiplicity of names for CLU is an indication of the complexity of the problem and could reflect, on one hand its multifunctionality, or alternatively could mask a commonality of function. The posited role for CLU, further supported as a cytoprotective prosurvival chaperone-like molecule, seems compelling, in contrast its tumor suppressor function, as a guide of the guardians of the genome (DNA-repair proteins Ku70/80, Bax cell death inducer), could really reflect the balanced expression of its different forms, most certainly depending on the intra- and extracellular microenvironment cross talk. The complicated balance of cytokines network and the regulation of CLU forms production in cancer and stromal cells undoubtedly represent a potential link among adaptative responses, genomic stability, and bystander effect after oxidative stresses and damage. This review focuses on the tumor-microenvironment interactions strictly involved in controlling local cancer growth, invasion, and distant metastases that play a decisive role in the regulation of CLU different forms expression and release. In addition, we focus on the pleiotropic action of the extracellular form of this protein, sCLU, that may play a crucial role in redirecting stromal changes, altering intercellular communications binding cell surface receptors and contributing to influence the secretion of chemokines in paracrine and autocrine fashion. Further elucidation of CLU functions inside and outside ("in and out") of cancer cell are warranted for a deeper understanding of the interplay between tumor and stroma, suggesting new therapeutic cotargeting strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CLU protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Clusterin, http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
pubmed:status
MEDLINE
pubmed:issn
0065-230X
pubmed:author
pubmed:issnType
Print
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-113
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
CLU "in and out": looking for a link.
pubmed:affiliation
Department of Biopathology, Institute of Anatomic Pathology, University of Rome Tor Vergata, 00133 Rome, Italy.
pubmed:publicationType
Journal Article, Review