Molecular interactions in cancer cell metastasis

Brooks, Susan A.; Lomax-Browne, Hannah J.; Carter, Tracey M.; Kinch, C.; Hall, Debbie

doi:10.1016/j.acthis.2008.11.022

Cited by 285 publications

(242 citation statements)

References 173 publications

Supporting

Mentioning

230

Contrasting

Unclassified

Order By: Relevance

“…41,42 In line with this, it has been reported that in gastric cancer, EGF both stimulates uPAR-expression and cell invasiveness through ERK and AP-1, as well as NF-kb signalling. 43,44 Furthermore, increased levels of TGF-b in gastric cancer have been associated with the stimulation of tumourpromoting myofibroblasts in addition to high uPA-levels in the tumour tissue. These findings were also associated with a poor prognosis for the patients.…”

Section: Discussionmentioning

confidence: 99%

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase‐type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high‐grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR‐immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR‐positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR‐score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR‐scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)‐stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR‐positive macrophages. Scoring of uPAR‐positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Tumor cell dissemination from the primary site to distant organs, such as the liver, involves complex phenotypic changes that enable cell detachment from the primary mass, cell migration, invasion of host tissues, extravasation and tumor cell adaptation to its changing microenvironment (reviewed in Steeg, 2006 andBrooks et al, 2009). The phenomenon of preferential homing of tumor cells (site-specific metastasis) has been recognized for decades but its molecular basis, particularly as it pertains to liver metastasis, is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

View full text Add to dashboard Cite

The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27 IGFÀIR murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen a1 and a2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/a2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by smallinterfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

show abstract

“…Tumor metastasis occurs through a multistep process (1). The interaction of circulating tumor cells that have detached from the primary tumor with structures of the tissue microvasculature is a crucial step preceding the invasion of the target organ.…”

mentioning

confidence: 99%

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

Lonsdorf

Kramer

Fahrleitner

et al. 2012

Journal of Biological Chemistry

101

View full text Add to dashboard Cite

A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothelium in vitro under shear conditions. Constitutively active platelet receptor GPIIb/IIIa (integrin ␣IIb␤3) expressed on Chinese hamster ovary cells promoted melanoma cell adhesion in the presence of fibrinogen, whereas blocking antibodies to a␤3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion to platelets. Furthermore, using intravital microscopy, we observed functional platelet-melanoma cell interactions, as platelet depletion resulted in significantly reduced melanoma cell adhesion to the injured vascular wall in vivo. Using a mouse model of hematogenous metastasis to the lung, we observed decreased metastasis of B16 melanoma cells to the lung by treatment with a mAb blocking the a subunit of a␤3 integrin. This effect was significantly reduced when platelets were depleted in vivo. Thus, the engagement of GPIIb/IIIa with a␤3 integrin interaction mediates tumor cell-platelet interactions and highlights how this interaction is involved in hematogenous tumor metastasis.

show abstract

Molecular interactions in cancer cell metastasis

Cited by 285 publications

References 173 publications

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

Contact Info

Product

Resources

About