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- Berta, Judit, et al.
(författare)
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Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
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| 2. |
- Schwendenwein, Anna, et al.
(författare)
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Molecular profiles of small cell lung cancer subtypes : therapeutic implications
- 2021
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Ingår i: Molecular Therapy - Oncolytics. - : Elsevier BV. - 2372-7705. ; 20, s. 470-483
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Forskningsöversikt (refereegranskat)abstract
- Small cell lung cancer (SCLC; accounting for approximately 13%–15% of all lung cancers) is an exceptionally lethal malignancy characterized by rapid doubling time and high propensity to metastasize. In contrast to the increasingly personalized therapies in other types of lung cancer, SCLC is still regarded as a homogeneous disease and the prognosis of SCLC patients remains poor. Recently, however, substantial progress has been made in our understanding of SCLC biology. Advances in genomics and development of new preclinical models have facilitated insights into the intratumoral heterogeneity and specific genetic alterations of this disease. This worldwide resurgence of studies on SCLC has ultimately led to the development of novel subtype-specific classifications primarily based on the neuroendocrine features and distinct molecular profiles of SCLC. Importantly, these biologically distinct subtypes might define unique therapeutic vulnerabilities. Herein, we summarize the current knowledge on the molecular profiles of SCLC subtypes with a focus on their potential clinical implications. Small cell lung cancer is still regarded as a homogeneous disease associated with poor prognosis. Recent analysis, however, has led to the development of novel subtype-specific classifications primarily based on the neuroendocrine features and molecular profiles. The better understanding of these biologically distinct subtypes might help to define unique therapeutic vulnerabilities.
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