Cancers, Vol. 9, Pages 133: Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?

Cancers, Vol. 9, Pages 133: Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?

Cancers doi: 10.3390/cancers9100133

Authors: Marion Lavergne Emily Janus-Bell Mathieu Schaff Christian Gachet Pierre Mangin

Platelets are small anucleated cell fragments that ensure the arrest of bleeding after a vessel wall injury. They are also involved in non-hemostatic function such as development, immunity, inflammation, and in the hematogeneous phase of metastasis. While the role of platelets in tumor metastasis has been recognized for 60 years, the molecular mechanism underlying this process remains largely unclear. Platelets physically and functionally interact with various tumor cells through surface receptors including integrins. Platelets express five integrins at their surface, namely α2β1, α5β1, α6β1, αvβ3, and αIIbβ3, which bind preferentially to collagen, fibronectin, laminin, vitronectin, and fibrinogen, respectively. The main role of platelet integrins is to ensure platelet adhesion and aggregation at sites of vascular injury. Two of these, α6β1 and αIIbβ3, were proposed to participate in platelet–tumor cell interaction and in tumor metastasis. It has also been reported that pharmacological agents targeting both integrins efficiently reduce experimental metastasis, suggesting that platelet integrins may represent new anti-metastatic targets. This review focuses on the role of platelet integrins in tumor metastasis and discusses whether these receptors may represent new potential targets for novel anti-metastatic approaches.

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Cancers, Vol. 9, Pages 133: Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?

Cancers, Vol. 9, Pages 133: Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?

Cancers doi: 10.3390/cancers9100133

Authors: Marion Lavergne Emily Janus-Bell Mathieu Schaff Christian Gachet Pierre Mangin

Platelets are small anucleated cell fragments that ensure the arrest of bleeding after a vessel wall injury. They are also involved in non-hemostatic function such as development, immunity, inflammation, and in the hematogeneous phase of metastasis. While the role of platelets in tumor metastasis has been recognized for 60 years, the molecular mechanism underlying this process remains largely unclear. Platelets physically and functionally interact with various tumor cells through surface receptors including integrins. Platelets express five integrins at their surface, namely α2β1, α5β1, α6β1, αvβ3, and αIIbβ3, which bind preferentially to collagen, fibronectin, laminin, vitronectin, and fibrinogen, respectively. The main role of platelet integrins is to ensure platelet adhesion and aggregation at sites of vascular injury. Two of these, α6β1 and αIIbβ3, were proposed to participate in platelet–tumor cell interaction and in tumor metastasis. It has also been reported that pharmacological agents targeting both integrins efficiently reduce experimental metastasis, suggesting that platelet integrins may represent new anti-metastatic targets. This review focuses on the role of platelet integrins in tumor metastasis and discusses whether these receptors may represent new potential targets for novel anti-metastatic approaches.

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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10⁻⁴; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10⁻⁹; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations. This article is protected by copyright. All rights reserved.

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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10⁻⁴; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10⁻⁹; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations. This article is protected by copyright. All rights reserved.

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Case 30-2017: A 65-Year-Old Woman with Altered Mental Status, Bacteremia, and Acute Liver Failure

Presentation of Case. Dr. Alexandra J. Coromilas (Medicine): A 65-year-old woman with autoimmune hepatitis and acute liver failure was transferred to this hospital for an evaluation for liver transplantation. The patient had been in her usual state of health until 6 years before this admission,…

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Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

pembrolizumabgougerot-sjrokentoxicityimmune related adverse events

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Bevacizumab + chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial - PRODIGE 20 study results

Abstract

BACKGROUND

Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific endpoints in this population.

PATIENTS AND METHODS

Patients aged 75 and over were randomly assigned to bevacizumab + chemotherapy (BEV) versus chemotherapy (CT). LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary endpoint, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.

RESULTS

102 pts were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary endpoint was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival (OS) was 21.7 months in BEV and 19.8 months in CT. The 36-months OS rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non hematologic toxicities (80.4% in BEV, 63.3% in CT).

CONCLUSION

Bevacizumab combined with chemotherapy was safe and efficient. Both arms met the primary safety and efficacy criteria.

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