title: Molecular changes in bone marrow, tumor and serum after conductive ablation of murine 4T1 breast carcinoma.
abstract: Thermal ablation of solid tumors using conductive interstitial thermal therapy (CITT) produces coagulative necrosis in the center of ablation. Local changes in homeostasis for surviving tumor and systemic changes in circulation and distant organs must be understood and monitored in order to prevent tumor re-growth and metastasis. The purpose of this study was to use a mouse carcinoma model to evaluate molecular changes in the bone marrow and surviving tumor after CITT treatment by quantification of transcripts associated with cancer progression and hyperthermia, serum cytokines, stress proteins and the marrow/tumor cross-talk regulator stromal-derived factor 1. Analysis of 27 genes and 22 proteins with quantitative PCR, ELISA, immunoblotting and multiplex antibody assays revealed that the gene and protein expression in tissue and serum was significantly different between ablated and control mice. The transcripts of four genes (Cxcl12, Sele, Fgf2, Lifr) were significantly higher in the bone marrow of treated mice. Tumors surviving ablation showed significantly lower levels of the Lifr and Sele transcripts. Similarly, the majority of transcripts measured in tumors decreased with treatment. Surviving tumors also contained lower levels of SDF-1α and HIF-1α proteins whereas HSP27 and HSP70 were higher. Of 16 serum chemokines, IFNγ and GM-CSF levels were lower with treatment. These results indicate that CITT ablation causes molecular changes which may slow cancer cell proliferation. However, inhibition of HSP27 may be necessary to control aggressiveness of surviving cancer stem cells. The changes in bone marrow are suggestive of possible increased recruitment of circulatory cancer cells. Therefore, the possibility of heightened bone metastasis after thermal ablation needs to be further investigated and inhibition strategies developed, if warranted.
authors.affiliation: Department of Radiation Oncology, University of Arkansas for Medical Science, Little Rock, AR, USA.
authors.forename: Beata D
authors.initials: BD
authors.lastname: Przybyla
authors.affiliation: Department of Cell Stress Biology and Otolaryngology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Gal
authors.initials: G
authors.lastname: Shafirstein
authors.affiliation: College of Medicine, University of Arkansas for Medical Science, Little Rock, AR, USA.
authors.forename: Sagar J
authors.initials: SJ
authors.lastname: Vishal
authors.affiliation: Geriatric Research Education and Clinical Center, Central Arkansas Veteran Healthcare System, Little Rock, AR, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dennis
authors.affiliation: Department of Radiation Oncology, University of Arkansas for Medical Science, Little Rock, AR, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006979:Hyperthermia, Induced; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger