Blockade of FLT4 suppresses metastasis of melanoma cells by impaired lymphatic vessels

Lee, Ji Yoon; Hong, Seok‐Ho; Shin, Minsang; Heo, Hye‐Ryeon; Jang, In Ho

doi:10.1016/j.bbrc.2016.08.017

Cited by 17 publications

(21 citation statements)

References 26 publications

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“…VEGF-C [18] IL-6 [19] Ring finger protein 180 [20] ID-1 [21] Sonic hedgehog [22] iNOS [23] Melanoma VEGF-C [24,25] FAS [24] Microphthalmia-associated transcription factor [25] c-Jun N-terminal kinase and p38/mitogen-activated protein kinase [25] Integrin α4β1 [26,27] FLT4 [28] High fat diet -CCL18, CCL21/CCR7 axis [ [34] Ezrin [34] COX-2 [35,38] Prostaglandin E2 and E receptor [35] NCoR and TRβ1 [36] TAMs [39,40] IL-24 [41] ELK3 [37] S1P [42] SEMA7a [43] DcR3 [44] Sulf2 [45] Mast cell density [46]…”

Section: Accepted Manuscript Cancer Markers Gastricmentioning

confidence: 99%

“…After activation of VEGFR-3, Homeobox transcription factor HOXD10 is activated, and is involved in lymphatic endothelial cell migration and formation of cord-like structures, as it regulates the expression of VE-cadherin, claudin-5, and nicotinamide adenine dinucleotide phosphate oxidase 3 (NOS3) [89]. Examples of cancers that have upregulated VEGF-C include melanoma, squamous cell carcinomas, gastric, cervical, breast, gallbladder, colon, lung, ovarian, chondrosarcoma, pancreatic, neuroblastoma, and prostate cancers [18][19][20]24,25,28,32,[34][35][36]41,47,50,51,54,55,59,62,63,71,90]. Many variables can increase VEGF-C expression in cancers.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Fms related tyrosine kinase 4 (FLT4) is a tyrosine kinase receptor for VEGF-C and VEGF-D that has been studied in melanoma, and it is important for lymphangiogenesis. When VEGF-C secreted by tumors binds to this receptor, lymphatic vessels can form, and tumor metastases may be initiated [28]. After administration of an FLT4 antagonist in a melanoma model, there was decreased tumor size and metastases in the lungs, fewer proliferative lymphatic vessels in the lungs in the intratumoral region, and a decrease in proliferating melanoma cells compared to untreated mice.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…IL-6 [19] Ring finger protein 180 [20] ID-1 [21] Sonic hedgehog [22] iNOS [23] Melanoma VEGF-C [24,25] FAS [24] Microphthalmia-associated transcription factor [25] c-Jun N-terminal kinase and p38/mitogen-activated protein kinase [25] Integrin α4β1 [26,27] FLT4 [28] High fat diet -CCL18, CCL21/CCR7 axis […”

Section: Conflict Of Interestmentioning

confidence: 99%

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Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Cote

Rao

Alany

et al. 2019

Advanced Drug Delivery Reviews

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Although many solid tumors use the lymphatic system to metastasize, there are few treatment options that directly target cancer present in the lymphatic system, and those that do are highly invasive, uncomfortable, and/or have limitations. This review gives a brief overview of lymphatic function and anatomy, discusses changes that befall the lymphatics in cancer and the mechanisms by which these changes occur, and presents limitations for drug delivery to the lymphatic system. We then go on to summarize relevant techniques and new research for targeting cancer populations in the lymphatics and enhancing drug delivery intralymphatically, including intralymphatic injections, isolated limb perfusion, passive nano drug delivery systems, and actively targeted nanomedicine.

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Section: Accepted Manuscript Cancer Markers Gastricmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Conflict Of Interestmentioning

confidence: 99%

See 2 more Smart Citations

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Cote

Rao

Alany

et al. 2019

Advanced Drug Delivery Reviews

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“…Analyzes to identify canonical pathways effected by CAL-101 treatment of the HMF and MRC5 cells was conducted by using secreted proteins differentially expressed in 28 comparison to CAL-101 treatment and the Ingenuity Pathway Analysis tool (https://www.qiagenbio-informatics.com/products/ingenuity-pathway-analysis).…”

Section: Functional Annotation Of Secreted Proteinsmentioning

confidence: 99%

Global kinome silencing combined with 3D invasion screening of the tumor microenvironment identifies fibroblast-expressed PIK3Cδ involvement in triple-negative breast cancer progression

Gagliano

Shah

Gargani

et al. 2019

Preprint

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As there is growing evidence for the tumor microenvironment's (TME) role in tumorigenesis, we sought to investigate the role of fibroblast-expressed kinases in triple negative breast cancer (TNBC). Using a high-throughput kinome screen combined with 3D invasion assays, we identified fibroblast-expressed PIK3Cδ (f-PIK3Cδ) as a key regulator of progression. Although PIK3Cδ has been mainly described in leucocytes, we detected high expression in primary fibroblasts derived from TNBC patients, while PIK3Cδ was undetectable in cancer epithelial cell lines. Genetic and pharmacologic gain-and loss-of functions experiments verified the contribution of f-PIK3Cδ in TNBC cell invasion. By employing an integrated secretomics and transcriptomics analysis, we revealed a paracrine mechanism via which f-PIK3Cδ confers its pro-tumorigenic effects. Inhibition of f-PIK3Cδ promoted the secretion of factors, including PLGF and BDNF, which subsequently led to upregulation of NR4A1 in TNBC cells where it acts as a tumor suppressor. Inhibition of PIK3Cδ in an orthotopic BC mouse model reduced tumor growth only after inoculation with fibroblasts, indicating a role of f-PIK3Cδ in cancer progression. Similar results were observed in the MMTV-PyMT transgenic BC mouse model, in addition to a decrease on tumor metastasis emphasizing the potential immune-independent effects of PIK3Cδ inhibition. Finally, analysis of BC patient cohorts and TCGA datasets identified f-PIK3Cδ (protein and mRNA levels) as an independent prognostic factor for overall and disease free survival, highlighting it as a therapeutic target for TNBC.

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Decoding the synergistic potential of MAZ‐51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals

Letsoalo,

Nortje,

Patrick

et al. 2024

Cell Biochemistry & Function

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Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment‐producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor‐beta 1 (TGF‐β1), vascular endothelial growth factor‐C (VEGF‐C) and C‐X‐C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3‐(4‐dimethylaminonaphthelen‐1‐ylmethylene)‐1,3‐dihydroindol‐2‐one) MAZ‐51 is an indolinone‐based molecule that inhibits VEGF‐C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR‐3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well‐being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun‐safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy.

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Blockade of FLT4 suppresses metastasis of melanoma cells by impaired lymphatic vessels

Cited by 17 publications

References 26 publications

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Global kinome silencing combined with 3D invasion screening of the tumor microenvironment identifies fibroblast-expressed PIK3Cδ involvement in triple-negative breast cancer progression

Decoding the synergistic potential of MAZ‐51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals

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