Expression of metalloproteases and their inhibitors in different histological types of breast cancer.
ABSTRACT Metalloproteases (MMPs) and their tissue inhibitors of metalloproteases (TIMPs) are involved in several key aspects of tumoral growth, invasion and metastasis. The purpose of this study was to characterize on how the different histological types of breast cancer differ in the expression of several components of this enzymatic system.
An immunohistochemical study was performed in 50 ductal, 23 lobular, 14 mucinous, 7 tubular, 4 papillary and 5 medullary invasive carcinomas, using tissue arrays and specific antibodies against 7 MMPs and 3 tisullar TIMPs. Staining results were categorized by means of a specific software program (score values).
Carcinomas of the ductal type showed higher score values for MMPs and TIMPs than the other histological types; whereas mucinous carcinomas had lower scores values for expressions of the majority of these proteins. Stromal fibroblasts were more frequently positive for MMP-1, -7 and -13 and TIMP-1 and -3, when present in carcinomas of the ductal type than in other histological types of breast carcinomas. Stromal mononuclear inflammatory cells were more frequently positive for MMP-1 and TIMP-3, but more often negative for MMP-7, -9 and -11, when located in carcinomas of the ductal type than in other histological types of breast carcinomas.
We found variations in MMP/TIMP expressions among the different histological subtypes of breast carcinomas suggesting differences in their tumor pathophysiology.
- [Show abstract] [Hide abstract]
ABSTRACT: Extracellular matrix (ECM) components, in addition to their structural functions, interact with cell surface receptors and intracellular components to modulate the transduction of signals for cell growth, differentiation, migration, proliferation, polarization, apoptosis and inflammation. Our previous findings in the gilthead seabream (Sparus aurata L.), a marine seasonal hermaphrodite teleost fish, have shown that both endocrine and immune stimuli modulate the expression of matrix metalloproteases (MMPs) and tissue inhibitors of MMP (TIMPs). In addition, collagen type I (COL1) induces the expression of some pro-inflammatory cytokines and MMPs in professional phagocytes. Consequently, in this study we use real-time RT-PCR to analyze the gene expression profile of several ECM-related molecules (MMP-2, -9 and -13, TIMP-2a, and -2b, COL1A1, and integrin beta1a) in different organs of adult specimens as well as in response to innate immune challenges. Our results showed that liver had the lowest basal levels of them, although they were clearly modulated during injury and infection. In the same way, ECM-related molecules seem to participate in pro-inflammatory processes, being of particular interest COL1 which is synthesized by immune cells and is able to act as autocrine/paracrine stimulus for them. Lastly, we propose that the observed correlations between ECM-related molecules during the inflammatory response should be considered to obtain a more accurate picture of their roles in this process.Developmental and comparative immunology 10/2010; 34(10):1051-8. DOI:10.1016/j.dci.2010.05.007 · 3.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The purpose of the present study was to examine the pathobiological properties of a matrix metalloproteinase, MMP-11 (also known as stromelysin-3), in the carcinogenesis of lobular carcinoma of the breast. Immunohistochemical staining demonstrated immunoreactivity with specific antibody to MMP-11 in 16 of 30 lobular carcinoma cells, but not in the non-cancerous terminal duct lobular unit. In positive cases, both noninvasive and invasive cancer cells exhibited immunoreactivity with anti-MMP-11 antibody; however, the staining patterns in noninvasive and invasive foci were distinct. In the noninvasive foci, immunoreactivity was observed in the cytoplasm beneath the plasma membrane, whereas immunoreactivity was found in all of the cytoplasm of infiltrating lobular carcinoma cells. Enforced expression of MMP-11 in the cultured lobular carcinoma MDA-MB-330 cells did not affect cell growth or Matrigel invasion activity. By contrast, overexpression of MMP-11 significantly increased resistance to anoikis, a programmed cell death triggered by a lack of proper cell matrix interaction, as evidenced by decrease in annexin V-positive cells and apoptotic DNA ladders. The present findings indicate that MMP-11 is overexpressed in many lobular carcinoma cells and that it may play a role in lobular carcinogenesis through increasing resistance to anoikis.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2011; 459(3):291-7. DOI:10.1007/s00428-011-1125-7 · 2.56 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Breast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed. Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes. Immunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise. Positive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes. The most important finding of this study was the independent prognostic value of MMP-1 as well as Ki-67 and bcl-2 expression in tumour cells. Our study showed also that both tumoural and stromal MMP-1 expression is associated with breast tumour progression and poor prognosis. A significant difference of MMP-1 expression by cancer associated stromal cells in luminal A, luminal B and triple-negative breast cancer classes was also demonstrated.BMC Cancer 08/2011; 11(1):348. DOI:10.1186/1471-2407-11-348 · 3.32 Impact Factor