A multigenic program mediating breast cancer metastasis to bone

Kang, Yibin; Siegel, Peter M.; Shu, Weiqun; Drobnjak, Marija; Käkönen, Sanna Maria; Cordon‐Cardo, Carlos; Guise, Theresa A.; Massagué, Joan

doi:10.1016/s1535-6108(03)00132-6

Cited by 2,345 publications

(2,386 citation statements)

References 45 publications

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“…Not only MMP-2 has pro-invasive activities, but also MMP-1 overexpression has been shown in a variety of advanced carcinomas, being associated with poor prognosis (Murray et al, 1998a, b;Ito et al, 1999;Fujimoto et al, 2008;Okuyama et al, 2008). High levels of MMP-1 expression have been detected in human breast cancer cells with elevated metastatic capacity towards the bone, providing evidence for its role in cancer cell invasion and metastasis (Kang et al, 2003;Okuyama et al, 2008). However, the molecular mechanism by which P-cadherin expression induces the secretion of these both enzymes to the medium remains unsolved.…”

Section: Discussionmentioning

confidence: 99%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.

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Section: Discussionmentioning

confidence: 99%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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“…Accumulating evidence suggests that metastasis of tumors to specific organs can be aided by interactions between chemokine receptors on cancer cells and their ligands in the target organs. For example, CXCR4 stimulates metastasis of breast cancer to the bone and lung where its ligand CXCL12 is abundant (Mu¨ller et al, 2001;Kang et al, 2003). We have recently shown that CXCR3 is responsible for LN metastasis of mouse melanoma cells B16F10, without affecting that to the lung (Kawada et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

et al. 2007

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Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA ('DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (Po0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.

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“…Interestingly, the DNA fragments responsible for these effects did not code directly for OPN protein, or even for any protein, rather they acted as competitors for binding of the transcription factor TCF-4, which suppresses OPN expression. Finally, while studies correlating elevated OPN expression with increased malignancy of a variety of cell lines are too numerous to list here, recently several groups have noted elevated OPN expression associated with the metastatic phenotype following selection and expression profiling of metastatic and nonmetastatic variants of human breast cancer cells (Urquidi et al, 2002;Kang et al, 2003).…”

Section: Opn In Tumorigenesis: Animal Studiesmentioning

confidence: 99%

Role of osteopontin in tumour progression

2004

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Since its first identification as a transformation-associated protein, osteopontin (OPN) has been recognised as important in the processes of tumorigenicity and metastasis. Here, we review the evidence that OPN might be considered as a candidate prognostic marker in human cancer. In animal systems, evidence from cell injection experiments and genetically manipulated mice suggest an important but complex role for the protein in tumour progression. Moreover, studies in a variety of human cancers associate high levels of OPN expression in tumours or in blood with more advanced cancers. The mechanism of action of OPN in promoting cancer is still unclear, and we consider aspects of OPN biology that can complicate interpretation of human studies. Nevertheless, growing evidence supports a role for OPN as a potential prognostic factor for various human cancers.

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A multigenic program mediating breast cancer metastasis to bone

Cited by 2,345 publications

References 45 publications

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

Role of osteopontin in tumour progression

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