Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast

Min, Kyueng‐Whan; Kim, Dong-Hoon; Im, Sung Il; Kim, Kyungeun; Lee, Hyun Joo; Chae, Seoung Wan; Sohn, Jin Hee; Pyo, Jung‐Soo; Oh, Yu Whan; Kim, Wan-Seop; Lee, So‐Young; Oh, Sukjoong; Choi, Sang‐Hoon; Park, Yong Lai; Park, Chan Heun

doi:10.1111/apm.12285

Cited by 35 publications

(31 citation statements)

References 34 publications

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“…This fits with the recent finding that MMP-2 in breast cancer metastasis is predominantly expressed in the tumor stroma, and that MMP-2 plays an important role in breast cancer tumor growth, progression, and metastasis [25]. Furthermore, stromal MMP-2 expression has been closely associated with different clinicopathologic parameters and overall survival of breast cancer patients [26]. Thus, co-localization of ADSCs and BRCAs might increase BRCA malignant progression in vivo by increasing the overall level of MMP-2.…”

Section: Discussionsupporting

confidence: 89%

The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction

Koellensperger

Bonnert²,

Zoernig

et al. 2017

Stem Cell Res Ther

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BackgroundIn this study we evaluated the interactions of human adipose tissue-derived stem cells (ADSCs) and different human breast cancer cell lines (BRCAs) with regard to the safety of cell-assisted lipotransfers for breast reconstruction and a thereby unintended co-localization of ADSCs and BRCAs.MethodsADSCs were co-cultured with five different human BRCAs (MCF-7, MDA-MB-231, SK-BR-3, ZR-75-30, and EVSA-T) and primary BRCAs from one patient in a transwell system, and cell-cell-interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real-time polymerase chain reaction (PCR) of more than 300 tumor-associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs). Results of co-culture were compared to those of the respective monoculture.ResultsQuantitative real-time PCR revealed remarkable changes in the expression of multiple tumor-associated genes in co-culture compared to monocultures of both ADSCs and BRCAs. Concomitantly, the concentration of several tumor-associated proteins, such as cytokines and MMPs, were strongly increased in co-culture. Furthermore, exclusively in co-culture with ADSCs, the different BRCAs were exposed to several important tumor-modulating proteins, such as CCL2, HGF, or interleukins.Co-culture did not significantly affect cellular proliferation of either ADSCs or BRCAs (p > 0.05). The migration of MCF-7 and MDA-MB-231 BRCAs was significantly increased in co-culture with ADSCs by a mean of 11% and 23%, respectively (p = 0.04 and 0.012), as well as that of ADSCs in co-culture with MDA-MB-231, ZR-75-30, and EVSA-T (+11–15%, p = 0.035–0.045). Co-culture with MDA-MB-231, SK-BR-3, and EVSA-T BRCAs significantly increased the invasive behavior of ADSCs by a mean of 24–41% (p = 0.014–0.039). There were no significant differences in the in vitro invasive properties of BRCAs in co-culture compared to monoculture. An in vitro angiogenesis assay revealed an increased tube formation of conditioned media from co-cultured BRCAs and ADSCs compared to the respective monocultures.ConclusionThis study further elucidates the possible interactions of primary human ADSCs with human BRCAs, pointing towards a potential increased oncological risk which should not be neglected when considering a clinical use of cell-assisted lipoaspirates in breast reconstruction.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0579-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction

Koellensperger

Bonnert²,

Zoernig

et al. 2017

Stem Cell Res Ther

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“…The results showed that overexpression of WNT5B significantly increased the invasive and metastatic ability of the COLO 205 cells in vitro. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases (16,17), play an important role in proteolytic degradation of the basement membrane and extracellular matrix (ECM), which is the initial step of tumor invasion and metastasis. In particular, MMP 2 and MMP 9 have been considered to be associated with increased invasiveness in various cancer cells (18).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway

et al. 2016

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WNT5B is a member of the WNT family that has been reported to be overexpressed in a variety of cancer cell lines and tissues, including colorectal cancer (CRC). However, the potential roles of WNT5B in tumorigenesis have not been reported. In the present study, the WNT5B gene was transfected into CRC cells and generated a COLO 205 cell line with stable overexpression of WNT5B. MTT, wound healing and Transwell assays showed that overexpression of WNT5B significantly increased cell proliferation, migration and invasion capacities of the COLO 205 cells in vitro. Meanwhile, western blotting demonstrated that cells with stable expression of WNT5B showed increased protein expression levels and activities of matrix metalloproteinase (MMP) 2 and MMP 9. In addition, we also observed activation of the WNT/JNK signaling pathway in WNT5B-overexpressing cells. Subsequently, c-jun NH2-terminal kinase (JNK) was knocked down by RNA interference in the WNT5B-overexpressing COLO 205 cells. Knockdown of JNK significantly reduced the migratory capacity of the COLO 205 cells and decreased protein expression levels and activities of MMP 2 and 9 in vitro. In conclusion, our findings suggest that WNT5B may play an important role in the tumorigenesis of CRC.

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“…). The role of active MMP‐2/9 in neoangiogenesis, tumor cell invasion and metastasis is well established …”

Section: Introductionmentioning

confidence: 99%

Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers

Sharma

2018

Intl Journal of Cancer

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ANX A2 is an important member of annexin family of proteins expressed on surface of endothelial cells (ECs), macrophages, mononuclear cells and various types of cancer cells. It exhibits high affinity binding for calcium (Ca ) and phospholipids. ANX A2 plays an important role in many biological processes such as endocytosis, exocytosis, autophagy, cell-cell communications and biochemical activation of plasminogen. On the cell surface ANX A2 organizes the assembly of plasminogen (PLG) and tissue plasminogen activator (tPA) for efficient conversion of PLG to plasmin, a serine protease. Proteolytic activity of plasmin is required for activation of inactive pro-metalloproteases (pro-MMPs) and latent growth factors for their biological actions. These activation steps are critical for degradation of extracellular matrix (ECM) and basement proteins (BM) for cancer cell invasion and metastasis. Increased expression of ANX A2 protein/gene has been correlated with invasion and metastasis in a variety of human cancers. Moreover, clinical studies have positively correlated ANX A2 protein expression with aggressive cancers and with resistance to anticancer drugs, shorter disease-free survival (DFS), and worse overall survival (OS). The mechanism(s) by which ANX A2 regulates cancer invasion and metastasis are beginning to emerge. Investigators used various technologies to target ANX A2 in preclinical model of human cancers and demonstrated exciting results. In this review article, we analyzed existing literature concurrent with our own findings and provided a critical overview of ANX A2-dependent mechanism(s) of cancer invasion and metastasis.

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Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast

Cited by 35 publications

References 34 publications

The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction

The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction

Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway

Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers

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