αvβ5-Integrins mediate early steps of metastasis formation

Enns, Andreas; Korb, Timo; Schlüter, Kerstin; Gaßmann, Peter; Spiegel, Hans‐Ullrich; Senninger, N.; Mitjans, Francesc; Haier, Jörg

doi:10.1016/j.ejca.2004.12.031

Cited by 66 publications

(116 citation statements)

References 42 publications

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“…19,20 Similarly, Kikkawa and colleagues 35 described an increased arrest of CHO cells within sinusoids if they injected cells transfected de novo with ␣v␤3-integrins. Wang and colleagues 36 reported that inhibition of ␣3␤1-integrins can reduce metastatic tumor cell arrest of HT-1080 fibrosarcoma cells within the lung microvessels.…”

Section: Discussionmentioning

confidence: 99%

“…Relative migration rates were calculated as percentage of cells within the host organ parenchyma in relation to the total number of observed cells. 19,20 In case of the pulmonary microcirculation, we were unable to differentiate between adherent and migrated cells, and therefore the numbers of arrested cells were counted in this organ. For the differentiation of free moving and rolling tumor cells, we tried to use the formula that was introduced by Ley and Gaehtgens 24,25 for the description of leukocyte behavior.…”

Section: In Vivo Observation Of Metastatic Tumor Cell Adhesionmentioning

confidence: 99%

“…These specific adhesive interactions were independent from the route of cell application, and tumor cells showed similar behavior within the liver sinusoids, if they were injected intravenously, intra-arterially, or intraportally. 18 Furthermore, using this model we previously showed that specific cell adhesions mediated by different integrins and selectin ligands at the tumor cell surfaces appear to be required for successful tumor cell arrest within the hepatic microcirculation, 19,20 with tumor cell adhesion modulated by the integrity of cytoskeletal components. 21 This observation of specific adhesive interactions within the hepatic microcirculation suggested an involvement of this step in the organ-specificity of metastasis formation.…”

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Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Schlüter

Gaßmann

Enns

et al. 2006

The American Journal of Pathology

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Adhesive and invasive characteristics appear to be crucial for organ-specific metastasis formation. Using intravital microscopy we investigated the relation between the metastatic potential of colon carcinoma cells and their adhesive and invasive behavior during early steps of metastasis within microvasculatures of rat liver, lung, intestine, skin, muscle, spleen, and kidney in vivo. Colorectal carcinomas will affect ϳ6% of the population in the Western countries during their lifetime. These carcinomas are the third leading cause of cancer-related deaths among women and men and are the most important malignancies of the gut.1 Approximately 50% of the cancer patients die within 5 years because of cancerrelated problems, mostly attributable to metastatic lesions caused by the spread of cancers to near and distant sites. Even after potentially curative surgery, more than 30% of the patients with colorectal carcinomas subsequently develop metastases demonstrating that the spread from primary tumors to distant organs is usually the life-limiting aspect in colorectal carcinoma patients. 2Similar to other cancer entities, colorectal carcinomas often show organ preference of metastasis formation. The liver is the most common organ in which colorectal carcinomas establish distant metastases, and the liver is involved in more than 70% of patients with colorectal metastases. However, in 40 to 50% of these patients with liver metastases, other organs are also involved in metastatic colonization. The second most important organ for colorectal cancer metastasis is the lung, and 20 to 30% of all distant colorectal carcinoma metastases are found primarily in the lung. Isolated lung metastases with no evidence of other organ involvement are found in 5 to 10% of colorectal cancer patients. Other organs, such as the central nervous system, adrenal glands, spleen, skeleton, or skin together account for less than 10% of all colorectal metastases. 2,3The metastatic process consists of a number of sequential, interrelated steps that can all be rate limiting. 4,5 An important and early step during formation of distant metastasis appears to be the arrest of circulating tumor cells within the host organ.6,7 Approximately a century ago, two major hypotheses on the mechanisms of tumor cell arrest in metastatic host organs were proposed. Ewing 8 assumed that the random mechanical lodgment of Supported by the Innovative Medizinische Forschung Fund (University Hospital Mü nster) (Ha 1 2 01 01 to J.H.).K.S. and P.G. contributed equally to this study.

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Section: Discussionmentioning

confidence: 99%

Section: In Vivo Observation Of Metastatic Tumor Cell Adhesionmentioning

confidence: 99%

mentioning

confidence: 99%

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Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Schlüter

Gaßmann

Enns

et al. 2006

The American Journal of Pathology

Self Cite

127

112

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“…The formation of liver metastasis is correlated with α v β 3 -and α v β 5 -integrin expression (33,34), binding to vitronectin and fibronectin, respectively. Kikkawa et al revealed that α v β 3 -integrin-expressing CHO-K1 cells were present in the extravascular region of the liver 24 h after portal vein injection, whereas α v β 3 -integrin-expressing CHO-K1 cells failed to adhere to sinusoidal endothelial cells, suggesting that the vitronectin receptor may solely promote the transendothelial migration step (33).…”

Section: Regulation By Cellular Adhesion Moleculesmentioning

confidence: 99%

Mechanisms regulating colorectal cancer cell metastasis into liver (Review)

Jin¹,

Weili

Lu³

et al. 2011

Oncology Letters

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Abstract. The metastatic spread of tumor cells is one of the most common causes of mortality in cancer patients. The elucidation of the molecular mechanisms that underlie the formation of metastatic colonies has been one of the major objectives of cancer research. Organ-specific colonization of cancer cells is a significant and noteworthy feature of metastasis. Colorectal cancer (CRC) is one of the most common causes of cancerrelated mortality. The liver is commonly the sole site of metastasis for CRC and represents a major cause of mortality in CRC patients. However, what regulates CRC cell metastasis into liver and the reasons for the liver-specific metastasis of CRC have yet to be adequately elucidated. Recent progress provides indications and a conceptual framework with which to investigate this issue. This review evaluated experimental and clinical evidence to support a mechanistic role for circulation patterns and microvessels in liver, metastasis-related genes, chemokines and their receptors, and cellular adhesion molecules in the process of CRC liver metastasis.

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“…In a later study, both a v h 3 and a v h 5 were not essential for tumor growth and progression, although they might play some role in mammary gland development (18,21). Moreover, a v h 5 integrins can mediate early steps of metastasis formation (22).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody 14C5 targets integrin αvβ5

Burvenich¹,

Schoonooghe

Vervoort³

et al. 2008

Molecular Cancer Therapeutics

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This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (A 1 , A 2 , A 3 , A v , B 1 , B 2 , B 3 , and B 4 ) and three integrin heterodimers (A v and lung (n = 16) cancer tissues. The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non -small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin A v B 5 , suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-A v B 5 -based therapies. [Mol Cancer Ther 2008;7(12):3771 -9]

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αvβ5-Integrins mediate early steps of metastasis formation

Cited by 66 publications

References 42 publications

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Mechanisms regulating colorectal cancer cell metastasis into liver (Review)

Monoclonal antibody 14C5 targets integrin αvβ5

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