title: Inhibition of tumor growth and alteration of associated macrophage cell type by an HO-1 inhibitor in breast carcinoma-bearing mice.
abstract: Heme oxygenase-1 [HO-1, also called heat shot protein 32 (HSP32)] can specifically metabolize heme to carbon monoxide, biliverdin, and ferrous iron and plays an important role in the processes of anti-inflammation, tissue protection, and antioxidative stress reaction. It has been reported that HO-1 can promote tumorigenesis and metastasis of many tumors. However, the detailed mechanisms of how HO-1 affects tumor progress are not clear. Here, we used ZnPPIX (a specific inhibitor of HO-1) to evaluate its potential effects on mouse breast cancer and tumor-associated macrophages (TAMs). We found out that mouse 4T1 breast cancer growth can be effectively suppressed through inhibition of HO-1 in vitro and in vivo. Moreover, in the 4T1 mouse model, when HO-1 was suppressed in TAMs, alternatively activated macrophages (M2 type) switched to classically activated macrophages (M1 type). In conclusion, 4T1 breast cancer growth was modulated by HO-1 expression. Furthermore, inhibition of HO-1 may induce tumor-associated immune response by activating TAMs' alternative proliferation. These data suggest that HO-1 may be an important target of breast cancer treatment.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Cheng Du, Sichuan, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Deng
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Ting-Hong
authors.initials: TH
authors.lastname: Ye
authors.forename: Guo-Bo
authors.initials: GB
authors.lastname: Shen
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zhao
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Sang
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Duan
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D011524:Protoporphyrins / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse