title: Recombinant Arabidopsis HSP70 Sustains Cell Survival and Metastatic Potential of Breast Cancer Cells.
abstract: The chaperone HSP70 protein is widely present in many different tumors and its expression correlates with an increased cell survival, low differentiation, and poor therapeutic outcome in human breast cancer. The intracellular protein has prevalently a cytoprotective function, while the extracellular HSP70 mediates immunologic responses. Evolutionarily, HSPs are well conserved from prokaryotes to eukaryotes, and human HSP70 shows a strong similarity to that of plant origin. In the current article, we have tested the potential effect of recombinant HSP70, from Arabidopsis thaliana, on cell survival and metastatic properties of breast cancer cells. Our data show that HSP70 sustains cell viability in MCF-7 and MDA-MB-231 breast tumoral cells and increases Cyclin D1 and Survivin expression. The extracellular HSP70 triggers cell migration and the activation of MMPs particularly in MDA-MB-231 cells. Furthermore, under UV-induced stress condition, the low levels of phospho-AKT were increased by exogenous HSP70, together with the upregulation of Cyclin D1, particularly in the tumoral cell phenotype. On the other hand, UV increased TP53 expression, and the coincubation of HSP70 lowers the TP53 levels similar to the control. These findings correlate with the cytoprotective and antiapoptotic role of HSPs, as reported in different cellular contexts. This is the first study on mammary cells that highlights how the heterologous HSP70 from Arabidopsis thaliana sustains cell survival prevalently in breast cancer cell types, thus maintaining their metastatic potential. Therefore, targeting HSP70 would be of clinical importance since HSP70 blocking selectively targets tumor cells, in which it supports cell growth and survival. Mol Cancer Ther; 15(5); 1063-73. ©2016 AACR.
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nigro
authors.affiliation: Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Mauro
authors.affiliation: Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giordano
authors.affiliation: Health Center, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panza
authors.affiliation: ALSIA-Research Center Metapontum Agrobios, Metaponto, Matera, Italy.
authors.forename: Rina
authors.initials: R
authors.lastname: Iannacone
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, Aldo Moro University, Bari, Italy.
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Liuzzi
authors.affiliation: Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende (CS), Italy. Health Center, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
authors.affiliation: Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende (CS), Italy. Health Center, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.affiliation: ALSIA-Research Center Metapontum Agrobios, Metaponto, Matera, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cellini
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Indiveri
authors.affiliation: Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende (CS), Italy. mamissina@yahoo.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Panno
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D014466:Ultraviolet Rays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018840:HSP70 Heat-Shock Proteins; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins