Progression of Metastasis through Lymphatic System

Zhou, Hengbo; Lei, Pin‐Ji; Padera, Timothy P.

doi:10.3390/cells10030627

Cited by 69 publications

(64 citation statements)

References 199 publications

(153 reference statements)

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“…For instance, STAT3 favors the spread of melanoma cells to distant organs, and it is particularly expressed in the melanoma metastasis 53,54 . For this reason, the identification of the IL-1α -STAT3 axis, able to address efficiently metastases at their first stage, gains particular clinical relevance 48,71 .…”

Section: Discussionmentioning

confidence: 99%

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

Virgilio

Bordini

Sartori

et al. 2021

Preprint

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During melanoma metastasization, tumor cells originated in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN) in a process that facilitates their spread across the body. Here, we characterized the innate inflammatory responses to melanoma metastasis in the sLN. For this purpose, we confirmed the migration of fluorescent metastatic melanoma cells to the sLN and we characterized the inflammatory response in the metastatic microenvironment. We found that macrophages located in the subcapsular sinus (SSM), produce pro-tumoral IL-1α after recognition of tumor antigens. Moreover, we confirmed that the administration of an anti-IL-1α depleting antibody reduced metastasis. Conversely, the administration of recombinant IL-1α accelerated the lymphatic spreading of the tumor. Additionally, the elimination of the macrophages significantly reduced the progression of the metastatic spread. To understand the mechanism of action of IL-1α in the context of the lymph node microenvironment, we applied single-cell RNA sequencing to dissected metastases obtained from animals treated with an anti-IL-1α blocking antibody. Amongst the different pathways affected, we identified STAT3 as one of the main targets of IL-1α signaling in metastatic cells. Moreover, we found that the anti-IL-1α anti-tumoral effect was not mediated by lymphocytes, as IL-1R1 KO mice did not show any improvement in metastasis growth. Finally, we found a synergistic anti-metastatic effect of the combination of IL-1α blocking and the STAT3 inhibitor (STAT3i) stattic. In summary, we described a new mechanism by which SSM support melanoma metastasis, highlighting a new target for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

Virgilio

Bordini

Sartori

et al. 2021

Preprint

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“…Indeed, cell migration is a crucial step in cancer progression, particularly in the tumor growth and metastasis processes [ 119 ]. In cancer progression, invasion and metastasis occur when tumor cells disseminate from the primary tumor spreading through the circulatory and lymphatic systems, invade across the basement membranes and endothelial walls, and colonize distant organs [ 120 ]. Metastasis is a very harmful feature of some cancers.…”

Section: Cancer Evaluation Modelsmentioning

confidence: 99%

Green Metallic Nanoparticles for Cancer Therapy: Evaluation Models and Cancer Applications

et al. 2021

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Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.

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“…This special arrangement mimics the arrangement of chylomicrons. The type of lipid used in lipid nanoparticles influences their absorption via transcellular route through intestinal epithelial cells which are polar in nature [47]. There are various types of lipid present like stearic acid, captopritol 888 ATO, tristerimn, monosterin and all these show different effect in and lymphatic uptake [48].…”

Section: Type Of Lipid Usedmentioning

confidence: 99%

Recent Advances in Nanoparticle Drug Delivery for Targeting Lymph Node -An Overview in Cancer Immunotherapy

Podutwar

Polshettiwar

Gawade

et al. 2021

JPRI

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Generally, it is said that the lymph node plays very important role in the cancer immunotherapy. So, delivering immunomodulating compounds to lymph node can be useful strategy for cancer immunotherapy. In case of this lymph node drug delivery system, lipid nanoparticles are widely used. High amount of drugs, nucleic acids and various other compounds can easily load in lipid nanoparticle, and they are easy to be manufacture on industrial scale also. In this review, we have focused on the potential of lipid nanoparticle technology to aim lymph nodes. However, there are many factors that control the delivery of drugs to lymphatics. Before the lymphatic detection, lipid nanoformulations are necessary to go through interstitial hindrance which alters delivery of them. So, the distribution and detection of lipid nanoformulations by means of lymphatic system depend on charge present on nanoparticles, hydrophobicity, particle size and molecular weight, form & type of lipid and emulsifier concentrations are as well significant factors disturbing the delivery of drugs in the lymphatic system.

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Progression of Metastasis through Lymphatic System

Cited by 69 publications

References 199 publications

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

Green Metallic Nanoparticles for Cancer Therapy: Evaluation Models and Cancer Applications

Recent Advances in Nanoparticle Drug Delivery for Targeting Lymph Node -An Overview in Cancer Immunotherapy

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