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Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells.

Liu B, Cui J, Sun J, Li J, Han X, Guo J, Yi M, Amizuka N, Xu X, Li M - Mol Med Rep (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

H&E staining, soft X-ray examination and immunohistochemical analyses of MGB1 and TRAP staining. (A) H&E staining and soft X-ray examination for breast cancer bone metastasis in tibiae. The metastatic tumor tissue occupied the majority of the spaces in the metaphysis and diaphysis. X-ray examination (lower right corner) revealed a radiolucent lesion in the tibia (white arrow). (Ba and Bb) Immunohistochemical analyses for MGB1 in the areas indicated by the yellow boxes in the (Aa) metaphysis and (Ab) diaphysis. Positive MGB1 staining (brown color) indicated metastatic breast cancer tissue. (Ca and b) Histochemical analysis of TRAP. Abundant TRAP-positive osteoclasts were found within the breast cancer metastasis nests and on the surface of the trabecular bone. Scale bars=250 µm for A; 50 µm for B and C. T, tumor cells; CB, cortical bone, *, normal bone marrow tissue; H&E, hematoxylin and eosin; MGB1, mammaglobin 1; TRAP, tartrate-resistant acid phosphatase.
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f1-mmr-14-02-1099: H&E staining, soft X-ray examination and immunohistochemical analyses of MGB1 and TRAP staining. (A) H&E staining and soft X-ray examination for breast cancer bone metastasis in tibiae. The metastatic tumor tissue occupied the majority of the spaces in the metaphysis and diaphysis. X-ray examination (lower right corner) revealed a radiolucent lesion in the tibia (white arrow). (Ba and Bb) Immunohistochemical analyses for MGB1 in the areas indicated by the yellow boxes in the (Aa) metaphysis and (Ab) diaphysis. Positive MGB1 staining (brown color) indicated metastatic breast cancer tissue. (Ca and b) Histochemical analysis of TRAP. Abundant TRAP-positive osteoclasts were found within the breast cancer metastasis nests and on the surface of the trabecular bone. Scale bars=250 µm for A; 50 µm for B and C. T, tumor cells; CB, cortical bone, *, normal bone marrow tissue; H&E, hematoxylin and eosin; MGB1, mammaglobin 1; TRAP, tartrate-resistant acid phosphatase.

Mentions: At 4 weeks post-intracardiac injection of MDA-MB-231 cells, 7/10 mice developed osteolytic lesions in the tibia, detected on soft X-ray examination (Fig. 1A; white arrow). Breast cancer cells positive for MGB1, which are exclusively overexpressed in primary and metastatic human breast cancer (22), were abundant in the metastatic lesions of the metaphysis (Fig. 1B) and diaphysis (Fig. 1C). The TRAP staining showed that several TRAP-positive multinucleate cells were present within the breast cancer bone metastasis nests and on the surface of trabecular bone (Fig. 1D and E).


Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells.

Liu B, Cui J, Sun J, Li J, Han X, Guo J, Yi M, Amizuka N, Xu X, Li M - Mol Med Rep (2016)

H&E staining, soft X-ray examination and immunohistochemical analyses of MGB1 and TRAP staining. (A) H&E staining and soft X-ray examination for breast cancer bone metastasis in tibiae. The metastatic tumor tissue occupied the majority of the spaces in the metaphysis and diaphysis. X-ray examination (lower right corner) revealed a radiolucent lesion in the tibia (white arrow). (Ba and Bb) Immunohistochemical analyses for MGB1 in the areas indicated by the yellow boxes in the (Aa) metaphysis and (Ab) diaphysis. Positive MGB1 staining (brown color) indicated metastatic breast cancer tissue. (Ca and b) Histochemical analysis of TRAP. Abundant TRAP-positive osteoclasts were found within the breast cancer metastasis nests and on the surface of the trabecular bone. Scale bars=250 µm for A; 50 µm for B and C. T, tumor cells; CB, cortical bone, *, normal bone marrow tissue; H&E, hematoxylin and eosin; MGB1, mammaglobin 1; TRAP, tartrate-resistant acid phosphatase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940081&req=5

f1-mmr-14-02-1099: H&E staining, soft X-ray examination and immunohistochemical analyses of MGB1 and TRAP staining. (A) H&E staining and soft X-ray examination for breast cancer bone metastasis in tibiae. The metastatic tumor tissue occupied the majority of the spaces in the metaphysis and diaphysis. X-ray examination (lower right corner) revealed a radiolucent lesion in the tibia (white arrow). (Ba and Bb) Immunohistochemical analyses for MGB1 in the areas indicated by the yellow boxes in the (Aa) metaphysis and (Ab) diaphysis. Positive MGB1 staining (brown color) indicated metastatic breast cancer tissue. (Ca and b) Histochemical analysis of TRAP. Abundant TRAP-positive osteoclasts were found within the breast cancer metastasis nests and on the surface of the trabecular bone. Scale bars=250 µm for A; 50 µm for B and C. T, tumor cells; CB, cortical bone, *, normal bone marrow tissue; H&E, hematoxylin and eosin; MGB1, mammaglobin 1; TRAP, tartrate-resistant acid phosphatase.
Mentions: At 4 weeks post-intracardiac injection of MDA-MB-231 cells, 7/10 mice developed osteolytic lesions in the tibia, detected on soft X-ray examination (Fig. 1A; white arrow). Breast cancer cells positive for MGB1, which are exclusively overexpressed in primary and metastatic human breast cancer (22), were abundant in the metastatic lesions of the metaphysis (Fig. 1B) and diaphysis (Fig. 1C). The TRAP staining showed that several TRAP-positive multinucleate cells were present within the breast cancer bone metastasis nests and on the surface of trabecular bone (Fig. 1D and E).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus