Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

The mechanisms of tumor metastasis to the sentinel lymph nodes are poorly understood. Vascular endothelial growth factor (VEGF)-A plays a principle role in tumor progression and angiogenesis; however, its role in tumor-associated lymphangiogenesis and lymphatic metastasis has remained unclear. We created transgenic mice that overexpress VEGF-A and green fluorescent protein specifically in the skin, and subjected them to a standard chemically-induced skin carcinogenesis regimen. We found that VEGF-A not only strongly promotes multistep skin carcinogenesis, but also induces active proliferation of VEGF receptor-2–expressing tumor-associated lymphatic vessels as well as tumor metastasis to the sentinel and distant lymph nodes. The lymphangiogenic activity of VEGF-A–expressing tumor cells was maintained within metastasis-containing lymph nodes. The most surprising finding of our study was that even before metastasizing, VEGF-A–overexpressing primary tumors induced sentinel lymph node lymphangiogenesis. This suggests that primary tumors might begin preparing their future metastatic site by producing lymphangiogenic factors that mediate their efficient transport to sentinel lymph nodes. This newly identified mechanism of inducing lymph node lymphangiogenesis likely contributes to tumor metastasis, and therefore, represents a new therapeutic target for advanced cancer and/or for the prevention of metastasis.

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Fatty acid oxidation: driver of lymph node metastasis

Cancer Cell International ◽

10.1186/s12935-021-02057-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mao Li ◽

Hong-chun Xian ◽

Ya-Jie Tang ◽

Xin-hua Liang ◽

Ya-ling Tang

Keyword(s):

Lymph Node ◽

Fatty Acid ◽

Lymph Node Metastasis ◽

Tumor Cells ◽

Fatty Acid Oxidation ◽

Tumor Metastasis ◽

Cancer Metabolism ◽

Acid Oxidation ◽

Node Metastasis

AbstractFatty acid oxidation (FAO) is the emerging hallmark of cancer metabolism because certain tumor cells preferentially utilize fatty acids for energy. Lymph node metastasis, the most common way of tumor metastasis, is much indispensable for grasping tumor progression, formulating therapy measure and evaluating tumor prognosis. There is a plethora of studies showing different ways how tumor cells metastasize to the lymph nodes, but the role of FAO in lymph node metastasis remains largely unknown. Here, we summarize recent findings and update the current understanding that FAO may enable lymph node metastasis formation. Afterward, it will open innovative possibilities to present a distinct therapy of targeting FAO, the metabolic rewiring of cancer to terminal cancer patients.

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Preclinical Models of Regional Lymph Node Tumor Metastasis

Cancer Metastasis And The Lymphovascular System: Basis For Rational Therapy - Cancer Treatment and Research ◽

10.1007/978-0-387-69219-7_10 ◽

2007 ◽

pp. 129-156 ◽

Cited By ~ 8

Author(s):

S. David Nathanson

Keyword(s):

Lymph Node ◽

Tumor Metastasis ◽

Regional Lymph Node ◽

Preclinical Models

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Abstract PR007: Lymph node colonization promotes distant tumor metastasis through the induction of systemic tumor-specific immunosuppression

10.1158/1538-7445.tme21-pr007 ◽

2021 ◽

Author(s):

Nathan E. Reticker-Flynn ◽

Weiruo Zhang ◽

Serena Chang ◽

Andrew J. Gentles ◽

John B. Sunwoo ◽

...

Keyword(s):

Lymph Node ◽

Tumor Metastasis ◽

Distant Tumor ◽

Specific Immunosuppression

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Correlation of expression of pro-apoptotic proteins bax and bak with lymph node metastasis in colonic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15042 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15042-e15042

Author(s):

R. A. Tracy ◽

S. T. Chuang ◽

J. Kim ◽

D. Coppola

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Odds Ratio ◽

Tumor Metastasis ◽

Patient Survival ◽

Tissue Microarrays ◽

Colonic Adenocarcinoma ◽

Node Metastasis ◽

Apoptotic Proteins ◽

Abc Method

e15042 Background: Colon cancer has been associated with disturbances in the regulation of apoptosis. Down regulation of Bax and Bak, members of the Bcl-2 family, are associated with tumor metastasis. Here we investigate how these two pro-apoptotic markers correlate with lymph node (LN) metastasis in colonic adenocarcinoma (CA). Methods: Paraffin-embedded sections from 100 cases of CA were constructed in tissue microarrays and subjected to immunohistochemistry (IHC) using the ABC method and antibodies for Bax and Bak. The IHC score is the product of intensity and percentage of positively stained cells, and ranged between 0 and 9. The total scores were divided into categories of “2 or less” and “3 or more.” These were than correlated with LN metastasis. Results: For Bax, 88 tumors were available while Bak was present in 100 tumors. In scoring Bax, 67 tumors had a score of ≤2 and 21 had a score of ≥3. Within the ≤2 category, 23 of 67 (34%) tumors had no LN metastases while 15 of 21 (71%) in the ≥3 category had no metastasis (p= 0.0029). For Bak staining, 23 had a score of ≤2 and 77 had a score of ≥3. Five of 23 (22%) tumors with a score ≤2 had no metastases and 35 of 77 (46%) with score ≥3 had no metastases (p= 0.0427). The LOGISTIC Procedure was used to show that a patient with a ≥3 Bax score has a 4.78 times odds ratio (95% C.I.: 1.64- 13.98) of having no metastases while a patient with a ≥3 Bak score has a 3 times odds ratio (95% C.I.: 1.01- 8.90) of having no metastases. Conclusions: We show correlation of the pro-apoptotic proteins Bax and Bak with decreased lymph node metastasis in CA. The findings suggest a role for these markers in predicting stage and patient survival in colonic adenocarcinoma. No significant financial relationships to disclose.

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