Altered Metastatic Behavior of Human Breast Cancer Cells after Experimental Manipulation of Matrix Metalloproteinase 8 Gene Expression

Montel, Valérie; Kleeman, Jeanine; Agarwal, Dianne; Spinella, Dominic G.; Kawai, Kanji; Tarin, David

doi:10.1158/0008-5472.can-03-2047

Cited by 100 publications

(86 citation statements)

References 45 publications

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“…MMP-8 null mice develop an increased incidence of skin tumors in a carcinogen-induced model of skin cancer, a finding that is likely due to these animals' increased inflammatory response to carcinogens (65). Similarly, overexpression of MMP-8 in metastatic breast cancer cells decreases their metastatic potential (66). Of note, such findings are not unique to MMP-8.…”

Section: Discussionmentioning

confidence: 99%

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Dangi-Garimella

Redig

Shields

et al. 2010

Journal of Biological Chemistry

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Matrix metalloproteinases (MMPs) 2 are a large family of highly conserved metalloendopeptidases with proteolytic activity directed against a variety of extracellular matrix (ECM) substrates (1-3). MMPs have been implicated in basement membrane proteolysis, activation of growth factors, and cleavage of cell-adhesion molecules. Extending mechanistic investigation to cancer biology, numerous studies have shown that MMP overexpression enhances the invasive activity of tumor cell lines (4 -6). Analysis of human disease further supports the pro-tumorigenic role of MMPs, as increased expression of these proteases in tumor samples is clinically associated with invasion, metastasis, poor prognosis, and shorter survival times (7,8). In the specific case of squamous cell carcinoma (SCC), increased expression of membrane type 1-MMP (MT1-MMP, MMP14) is associated with ECM breakdown, tissue invasion, and lymph node metastasis (8).However, several animal studies have now clearly demonstrated that multiple members of the MMP family provide a paradoxically protective effect during the relentless molecular destruction that characterizes malignant progression. MMPs may have been initially identified as potent pro-tumorigenic proteases, but their simultaneous ability to function in an opposing, anti-tumorigenic role is now equally well established (9, 10). Such data underscore both the complexity of MMP activity in cellular signaling events as well as the importance of stringently evaluating the context in which these proteases take on either an anti-tumorigenic or pro-tumorigenic role. Intriguingly, several recent studies using SCC models have begun to suggest a putative mechanism through which MMPs may be induced to function primarily as anti-tumorigenic proteases. When exposed to carcinogens, MMP3-null mice developed squamous cell skin cancers that not only grew faster but were also strikingly less differentiated than those of control animals (11). Significantly, orthotopic injection of MMP3-expressing tumor cells resulted in pronounced tumor cell differentiation (12). However, although such findings indicate that MMPs may inhibit SCC progression by promoting tumor cell differentiation, the precise mechanism through which these proteinases regulate this process has not yet been elucidated.In normal tissue keratinocyte differentiation is a complex process mediated by cell-ECM and cell-cell interactions that subsequently activate downstream signaling pathways (13-15). Specifically, among structural proteins, integrins mediate primarily cell-ECM interactions, whereas cadherins are responsible for cell-cell interactions (13). In vitro activation of integrins or inhibition of cadherins after ligation or dominant negative expression, respectively, results in negative regulation of human keratinocyte differentiation (16 -18). Furthermore, beyond structural proteins, Rho GTPases are also known to be an important component of keratinocyte differentiation pathways. Rho signaling has been shown to mediate cell-cell and cell-matrix adhesion...

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Section: Discussionmentioning

confidence: 99%

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Dangi-Garimella

Redig

Shields

et al. 2010

Journal of Biological Chemistry

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“…The details of the poorly or progressively highly metastatic behavior of the NM-2C5, M-4A4, LM-3 and CL16 lines in vivo have been documented previously. [20][21][22]25,26 The present study was conducted in duplicate in nude mice and in SCIDs to cross validate the findings and to focus the investigation on strain-independent interactions with the host environment, which influence metastasis.…”

Section: Cell Lines and Xenograft Modelmentioning

confidence: 99%

Tumor–stromal interactions reciprocally modulate gene expression patterns during carcinogenesis and metastasis

Montel

Mose

Tarin

2006

Intl Journal of Cancer

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This study used a unique xenogeneic breast cancer model to study the effects of tumor cells and neighboring host cells upon each other in tumor growth and metastasis. It exploited species differences between the interacting components to determine how the host influenced the tumor and vice versa. It was found that the gene expression profiles of highly and poorly metastatic clones from the same human breast carcinoma changed differentially when the cells were transferred from growth in vitro to the mammary gland. We describe novel sets of genes, validated by human-specific probes, which were induced in the 2 isogenic, but phenotypically different, tumor lineages by the mammary environment. Conversely, the tumor cells also induced changes in gene expression in the neighboring host stromal (i.e., mesenchymal) cell lineages, validated by mouse-specific probes. Reciprocal inductive interactions were also demonstrated in the tumor deposits formed preferentially in the lungs and lymph nodes by the highly metastatic tumor cells. Subtraction of the induced gene changes in the primary site from those in the metastases revealed that the number and magnitude of specific gene inductions in colonized organs were moderate. This finding indicates that the gene expression program causing metastasis has only limited flexibility and fits well with clinical observations that tumor cells form metastases preferentially in select organs, although tumor cells are scattered ubiquitously. This dependency on suitable host niches suggests new molecular therapeutic avenues that target genes in the host-support system that is manipulated by the malignant cells. To survive and prevail, the intruding cells must co-opt local conditions to provide their needs. This prompts questions about what interactions and mechanisms are activated to promote this disorderly behavior and how these are normally suppressed.The discoveries of Spemann and colleagues, 1 that cells of different embryonic lineages actively induce each other to cooperate in the formation of tissues, organs and body regions have far reaching applications in solving such fundamental but clinically relevant questions. Their findings provided a rational framework for explaining how specialized cell lineages interact to produce and maintain the anatomic plan of the whole animal and the microscopic architecture of its individual organs throughout life and healing processes. Conversely, their observations also have important implications for understanding mechanisms underlying the progressive histological disorganization which characterizes cancer pathogenesis and progression to metastatic malignancy. Important steps in recognizing the importance of cell and tissue interactions in neoplasia include the work of Orr that showed that morphological 2 and functional 3 changes occur in the dermis of carcinogen-treated skin long before a carcinoma develops from the overlying epidermis. Later, Grobstein 4 and Sengel et al. 5 showed that the formation of the microscopic anatomy and histology of org...

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“…Secondly, in two cell lines derived from wild-type MDA-MB-435 cancer cells, which display high (M-4A4) or low (NM-2C5) metastatic capacities, overexpression of MMP-8 would reduce the metastatic capacity of M-4A4 cells, whereas knockdown of MMP-8 gene would enhance the metastatic capacity of NM-2C5 cells (26,27). Thirdly, the rs11225395 C-799T single-nucleotide polymorphism (SNP) at the MMP8 promoter region may affect the expression levels of MMP-8 and associate with early-stage disease (28).…”

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confidence: 99%

The Contribution of Matrix Metalloproteinase-8 Promoter Polymorphism to Oral Cancer Susceptibility

Hung

Tsai

Shih

et al. 2017

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Altered Metastatic Behavior of Human Breast Cancer Cells after Experimental Manipulation of Matrix Metalloproteinase 8 Gene Expression

Cited by 100 publications

References 45 publications

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Tumor–stromal interactions reciprocally modulate gene expression patterns during carcinogenesis and metastasis

The Contribution of Matrix Metalloproteinase-8 Promoter Polymorphism to Oral Cancer Susceptibility

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