title: Human breast adenocarcinoma (MDA-231) and human lung squamous cell carcinoma (Hara) do not have the ability to cause bone resorption by themselves during the establishment of bone metastasis.
abstract: Osteolysis is an important process in the establishment of bone metastasis. The role which cancer cells play in this process is not fully understood. In this study, we first established a reproducible in vivo bone metastasis model using two types of tumor cells, human breast adenocarcinoma (MDA-231) and human lung squamous cell carcinoma (Hara cells), and examined in vitro characteristics of the tumor cells. Tumor cells injected into the left heart ventricle of nude mice preferentially metastasized to bone, 6 weeks after the inoculation. Histological observation of the bone metastatic lesion showed that tumor cells invaded the bone marrow, and osteoclasts adjacent to fibroblasts were actively resorbing the bone matrix. In vitro analysis of the tumor cells showed that MDA-231 cells express cathepsin K, matrix metalloproteinase 9 (MMP-9), and membrane type-1 matrix metalloproteinase (MT1-MMP), all of which are believed to play an important role in osteoclastic bone resorption. In contrast, Hara cells do not express cathepsin K and MT1-MMP. MMP-9 was expressed at a low level. To assess the osteolytic activity of the tumor cells, an in vitro pit assay was performed. The rabbit osteoclasts formed numerous pits on a dentin slice after 18 h of incubation, whereas tumor cells by themselves did not. Taken together, we conclude that MDA-231 and Hara cells, which metastasize to the bone in vivo, do not have enough ability to achieve bone resorption by themselves, but rather achieve it through activation of fibroblast like cells and osteoclasts.
authors.affiliation: Discovery Biology, Novartis Institute for BioMedical Research, Tsukuba, Ibaraki, Japan.
authors.forename: Amy
authors.initials: A
authors.lastname: Tomita
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kasaoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Inui
authors.forename: Minako
authors.initials: M
authors.lastname: Toyoshima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Saiki
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D001859:Bone Neoplasms / Q000556:secondary*; D001862:Bone Resorption / Q000209:etiology*; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology*; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14