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MMP-9 expression varies according to molecular subtypes of breast cancer.

Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA - BMC Cancer (2014)

Bottom Line: We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue.Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada. louis.gaboury@umontreal.ca.

ABSTRACT

Background: In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.

Methods: MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.

Results: Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

Conclusions: Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

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Related in: MedlinePlus

Expression of MMP-9 in normal breast tissue. (A) Normal breast lobule lacking MMP-9 expression in both luminal and myoepithelial cells. Adjacent stromal cells also fail to express MMP-9 (74% of the patients). (B) Normal breast tissue exhibiting faint expression of MMP-9 in the cytoplasm of luminal cells, myoepithelial cells and in a few stromal cells surrounding normal breast acini. A &B are two distinct normal breast tissue from the same TMA incubated with anti-MMP9 antibody. Magnification 40X (A&B), 63X inset in Figure 4B.
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Fig4: Expression of MMP-9 in normal breast tissue. (A) Normal breast lobule lacking MMP-9 expression in both luminal and myoepithelial cells. Adjacent stromal cells also fail to express MMP-9 (74% of the patients). (B) Normal breast tissue exhibiting faint expression of MMP-9 in the cytoplasm of luminal cells, myoepithelial cells and in a few stromal cells surrounding normal breast acini. A &B are two distinct normal breast tissue from the same TMA incubated with anti-MMP9 antibody. Magnification 40X (A&B), 63X inset in Figure 4B.

Mentions: Once all immunostaining conditions were satisfactorily established, we carried out IHC reactions on TMAs comprising both normal and neoplastic breast tissues. Our results indicate that 74% of normal breast tissues fail to express any MMP-9 reactivity in the luminal, myoepithelial cells and stromal cells surrounding normal breast ducts (Figure 4A). However, in a minority of normal breast tissues (26%) MMP-9 was faintly expressed and restricted to the cytoplasm of luminal, myoepithelial and a few adjacent stromal cells (Figure 4B). MMP-9 did not label either the nucleus nor the cell membrane of any of these cells. Notably, the level of MMP-9 expression in the luminal cells consistently exceeded that present in the adjacent stromal cells.Figure 3


MMP-9 expression varies according to molecular subtypes of breast cancer.

Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA - BMC Cancer (2014)

Expression of MMP-9 in normal breast tissue. (A) Normal breast lobule lacking MMP-9 expression in both luminal and myoepithelial cells. Adjacent stromal cells also fail to express MMP-9 (74% of the patients). (B) Normal breast tissue exhibiting faint expression of MMP-9 in the cytoplasm of luminal cells, myoepithelial cells and in a few stromal cells surrounding normal breast acini. A &B are two distinct normal breast tissue from the same TMA incubated with anti-MMP9 antibody. Magnification 40X (A&B), 63X inset in Figure 4B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150970&req=5

Fig4: Expression of MMP-9 in normal breast tissue. (A) Normal breast lobule lacking MMP-9 expression in both luminal and myoepithelial cells. Adjacent stromal cells also fail to express MMP-9 (74% of the patients). (B) Normal breast tissue exhibiting faint expression of MMP-9 in the cytoplasm of luminal cells, myoepithelial cells and in a few stromal cells surrounding normal breast acini. A &B are two distinct normal breast tissue from the same TMA incubated with anti-MMP9 antibody. Magnification 40X (A&B), 63X inset in Figure 4B.
Mentions: Once all immunostaining conditions were satisfactorily established, we carried out IHC reactions on TMAs comprising both normal and neoplastic breast tissues. Our results indicate that 74% of normal breast tissues fail to express any MMP-9 reactivity in the luminal, myoepithelial cells and stromal cells surrounding normal breast ducts (Figure 4A). However, in a minority of normal breast tissues (26%) MMP-9 was faintly expressed and restricted to the cytoplasm of luminal, myoepithelial and a few adjacent stromal cells (Figure 4B). MMP-9 did not label either the nucleus nor the cell membrane of any of these cells. Notably, the level of MMP-9 expression in the luminal cells consistently exceeded that present in the adjacent stromal cells.Figure 3

Bottom Line: We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue.Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada. louis.gaboury@umontreal.ca.

ABSTRACT

Background: In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.

Methods: MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.

Results: Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

Conclusions: Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

Show MeSH
Related in: MedlinePlus