Faculty Opinions recommendation of Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis.

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

Download Full-text

Abstract LB-422: Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis

10.1158/1538-7445.am2011-lb-422 ◽

2011 ◽

Author(s):

Tuomas Tammela ◽

Anne Saaristo ◽

Tanja Holopainen ◽

Seppo Ylä-Herttuala ◽

Leif C. Andersson ◽

...

Keyword(s):

Cancer Cells ◽

Lymphatic Vessels

Download Full-text

Tumor Lymphangiogenesis as a Potential Therapeutic Target

Journal of Oncology ◽

10.1155/2012/204946 ◽

2012 ◽

Vol 2012 ◽

pp. 1-23 ◽

Cited By ~ 47

Author(s):

Tam Duong ◽

Peter Koopman ◽

Mathias Francois

Keyword(s):

Lymph Node ◽

Cancer Cells ◽

Primary Tumor ◽

Molecular Mechanisms ◽

Patient Survival ◽

Regional Lymph Node ◽

Lymphatic Vessels ◽

Potential Therapeutic Target ◽

Tumor Lymphangiogenesis

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

Download Full-text

Human Tumor‐Lymphatic Microfluidic Model Reveals Differential Conditioning of Lymphatic Vessels by Breast Cancer Cells

Advanced Healthcare Materials ◽

10.1002/adhm.201900925 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1900925 ◽

Cited By ~ 7

Author(s):

Jose M. Ayuso ◽

Max M. Gong ◽

Melissa C. Skala ◽

Paul M. Harari ◽

David J. Beebe

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Differential Conditioning ◽

Breast Cancer Cells ◽

Lymphatic Vessels ◽

Human Tumor

Download Full-text

Evaluation of Variances in VEGF-A-D and VEGFR-1-3 Expression in the Ishikawa Endometrial Cancer Cell Line Treated with Salinomycin and An-ti-Angiogenic/Lymphangiogenic Effect

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200710093519 ◽

2020 ◽

Vol 21 ◽

Author(s):

Piotr Kras ◽

Karol Talkowski ◽

Beniamin Oskar Grabarek ◽

Nina Dziobek ◽

Dariusz Boroń ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Cells ◽

Expression Pattern ◽

Lymphatic Vessels ◽

Cancer Cell Line ◽

Control Culture ◽

Significant Difference ◽

Correct Pattern ◽

The Difference ◽

Endothelial Growth Factor

Background: In cancer, an excessive and uncontrolled process of creating new blood and lymphatic vessels that play a key role in the metastasis process can be observed. The vascular endothelial growth factor (VEGF-A,-B,-C,-D) family together with their specific receptors (VEGFR-1,-2,-3) plays a key role in these processes, therefore it would be reasonable to determine the correct pattern of their expression. Objective: The study aimed to assess the use of salinomycin as an anti-angiogenic and anti-lymphangiogenic drug during endometrial cancer by examining changes in the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, VEGFR-3 depending on the treatment period of the Ishikawa endometrial cancer cells with salinomycin in comparison to the control culture. Materials and Methods: To determine how influential salinomycin was on the expression of both mRNAs, 1 µM of the drug was added to the cell culture and then it was cultured all together for 12,24 and 48 hour periods. The cells that made up the control culture were not treated with salinomycin. To determine the changes in the expression profile of the selected genes we used the microarray, techniques: RTqPCR and ELISA (p<0.05). Results: For all isoforms of VEGF-A-D as well as receptors of VEGFR-1-3, a decrease in expression under the influence of salinomycin was noted. For VEGF-A and VEGFR-1, the difference in the expression between the culture treated with salinomycin in comparison to the control was statistically significant (p=0.0004). In turn for VEGF-B, the difference between the culture exposed for 24 hours in comparison to the control (p=0.00000) as well as the comparison between H48 vs C (p=0.00000) was statistically significant. In reference to VEGF-C, VEGFR-2, VEGFR-3 the statistical analysis showed the significant difference in expression between the culture incubated with the drug for 12,24 and 48 hours in comparison to the control as well as between the selected times. For all of these comparisons, p=0.00000 was utilized. Conclusions: Salinomycin changes the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3 in endometrial cancer cells. The obtained results suggest that salinomycin might exert the effect via VEGF signaling pathways.

Download Full-text

Regulation of lymphangiogenesis by extracellular vesicles in cancer metastasis

Experimental Biology and Medicine ◽

10.1177/15353702211021022 ◽

2021 ◽

pp. 153537022110210

Author(s):

Chu-An Wang ◽

Shaw-Jenq Tsai

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Lymphatic Metastasis ◽

Lymphatic Vessel ◽

Cancer Metastasis ◽

Lymphatic System ◽

Lymphatic Vessels ◽

Extracellular Vesicle ◽

Tissue Fluid ◽

Vessel Infiltration

Metastasis is not only one of the hallmarks of cancer but, unfortunately, it also is the most accurate biomarker for poor prognosis. Cancer cells metastasize through two different but eventually merged routes, the vasculature and lymphatic systems. The processes of cancer metastasis through blood vessel have been extensively studied and are well documented in the literature. In contrast, metastasis through the lymphatic system is less studied. Most people believe that cancer cells metastasize through lymphatic vessel are passive because the lymphatic system is thought to be a sewage draining system that collects whatever appears in the tissue fluid. It was recently found that cancer cells disseminated from lymphatic vessels are protected from being destroyed by our body’s defense system. Furthermore, some cancer cells or cancer-associated immune cells secrete lymphangiogenic factors to recruit lymphatic vessel infiltration to the tumor region, a process known as lymphangiogenesis. To ensure the efficiency of lymphangiogenesis, the lymphangiogenic mediators are carried or packed by nanometer-sized particles named extracellular vesicles. Extracellular vesicles are lipid bilayer particles released from eventually every single cell, including bacterium, with diameters ranging from 30 nm (exosome) to several micrometers (apoptotic body). Components carried by extracellular vesicles include but are not limited to DNA, RNA, protein, fatty acid, and other metabolites. Recent studies suggest that cancer cells not only secrete more extracellular vesicles but also upload critical mediators required for lymphatic metastasis onto extracellular vesicles. This review will summarize recent advances in cancer lymphatic metastasis and how cancer cells regulate this process via extracellular vesicle-dependent lymphangiogenesis.

Download Full-text

Use of a Lymphatic Drug Delivery System and Sonoporation to Target Malignant Metastatic Breast Cancer Cells Proliferating in the Marginal Sinuses

Scientific Reports ◽

10.1038/s41598-019-49386-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Shigeki Kato ◽

Yuko Shirai ◽

Maya Sakamoto ◽

Shiro Mori ◽

Tetsuya Kodama

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Breast Cancer Cells ◽

Lymphatic Vessels ◽

Metastatic Breast ◽

High Frequency Ultrasound ◽

Marginal Sinus ◽

Metastatic Cells ◽

Systemic Lymphadenopathy

Abstract Lymph node (LN) metastasis through the lymphatic network is a major route for cancer dissemination. Tumor cells reach the marginal sinuses of LNs via afferent lymphatic vessels (LVs) and form metastatic lesions that lead to distant metastasis. Thus, targeting of metastatic cells in the marginal sinuses could improve cancer treatment outcomes. Here, we investigated whether lymphatic administration of a drug combined with sonoporation could be used to treat a LN containing proliferating murine FM3A breast cancer cells, which are highly invasive, in its marginal sinus. First, we used contrast-enhanced high-frequency ultrasound and histopathology to analyze the structure of LVs in MXH10/Mo-lpr/lpr mice, which exhibit systemic lymphadenopathy. We found that contrast agent injected into the subiliac LN flowed into the marginal sinus of the proper axillary LN (PALN) and reached the cortex. Next, we examined the anti-tumor effects of our proposed technique. We found that a strong anti-tumor effect was achieved by lymphatic administration of doxorubicin and sonoporation. Furthermore, our proposed method prevented tumor cells in the marginal sinus from invading the parenchyma of the PALN and resulted in tumor necrosis. We conclude that lymphatic administration of a drug combined with sonoporation could exert a curative effect in LNs containing metastatic cells in their marginal sinuses.

Download Full-text

The lymphatic system and sentinel lymph nodes: conduit for cancer metastasis

Clinical & Experimental Metastasis ◽

10.1007/s10585-021-10123-w ◽

2021 ◽

Author(s):

Stanley P. Leong ◽

Alexander Pissas ◽

Muriel Scarato ◽

Francoise Gallon ◽

Marie Helene Pissas ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Cancer Cells ◽

Cancer Metastasis ◽

Lymphatic System ◽

Early Cancer ◽

Lymphatic Vessels ◽

Review Article ◽

Cancer Spread

AbstractThe lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.

Download Full-text

Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis

Frontiers in Oncology ◽

10.3389/fonc.2021.783309 ◽

2022 ◽

Vol 11 ◽

Author(s):

Chuqi Wang ◽

Ming Chu

Keyword(s):

Cancer Cells ◽

Lymphatic Metastasis ◽

Tumor Invasion ◽

Molecular Mechanisms ◽

Lymphatic Vessels ◽

The Body ◽

Regional Lymph Nodes ◽

Cancer Management ◽

The Past ◽

Tight Correlation

Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.

Download Full-text