Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells.
The aim of the present study was to investigate the expression of matrix metalloproteinase (MMP)9 and MMP2, and their potential roles in bone metastasis nests using a well-standardized model of breast cancer bone metastasis in nude mice. BALB/c nu/nu mice (5-week-old; n=10) were subjected to intracardiac injection of MDA-MB-231 human breast cancer cells. After 4 weeks, the mice exhibiting radiolucent lesions in tibiae were sacrificed, and the tibiae were removed for histochemical analysis. The gene expression of MMP2 and MMP9 in the tumor cells, metaphysis and diaphysis of normal BALB/c nu/nu mice were determined using reverse transcription-polymerase chain reaction analysis. The metastatic tumor tissue occupied almost the entire bone marrow cavity. Numerous tartrate-resistant acid phosphatase-positive osteoclasts were found in the metastasized lesions. The invaded tumor cells positive for mammaglobin 1 exhibited different proliferation activities and apoptosis between the metaphysis and diaphysis. Proliferating cell nuclear antigen was expressed at high levels in the metaphyseal area, whereas TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were more evident in the diaphysis area. Of note, MMP9 was expressed predominantly in the proliferating cell nuclear antigen‑positive area, whereas the expression of MMP2 was observed predominantly in the diaphysis, which had more TUNEL‑positive cells. Taken together, the results suggested that MMP9 and MMP2 may have their own importance in extracellular matrix degradation and trabecular bone damage in different zones of bone metastasis, including the metaphysis and diaphysis.
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Bo
B
Liu
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Jian
J
Cui
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Jing
J
Sun
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Juan
J
Li
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Xiuchun
X
Han
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Jie
J
Guo
Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaidō 060‑8638, Japan.
Min
M
Yi
Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaidō 060‑8586, Japan.
Norio
N
Amizuka
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Xin
X
Xu
Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.
Minqi
M
Li
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D060785:Mammaglobin A / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D010014:Osteolysis / Q000378:metabolism* / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism
D015415:Biomarkers; D060785:Mammaglobin A; D018809:Proliferating Cell Nuclear Antigen; C556448:SCGB2A2 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9