scholarly journals Progression of Metastasis through Lymphatic System

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 627
Author(s):  
Hengbo Zhou ◽  
Pin-ji Lei ◽  
Timothy P. Padera

Lymph nodes are the most common sites of metastasis in cancer patients. Nodal disease status provides great prognostic power, but how lymph node metastases should be treated is under debate. Thus, it is important to understand the mechanisms by which lymph node metastases progress and how they can be targeted to provide therapeutic benefits. In this review, we focus on delineating the process of cancer cell migration to and through lymphatic vessels, survival in draining lymph nodes and further spread to other distant organs. In addition, emerging molecular targets and potential strategies to inhibit lymph node metastasis are discussed.

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1507 ◽  
Author(s):  
Ginter ◽  
Karagiannis ◽  
Entenberg ◽  
Lin ◽  
Condeelis ◽  
...  

Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional “doorways” for hematogenous dissemination. Here, we studied a well-annotated case–control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels.


2011 ◽  
Vol 125 (8) ◽  
pp. 820-828 ◽  
Author(s):  
Y Shu ◽  
X Xu ◽  
Z Wang ◽  
W Dai ◽  
Y Zhang ◽  
...  

AbstractObjective:To investigate the performance of indirect computed tomography lymphography with iopamidol for detecting cervical lymph node metastases in a tongue VX2 carcinoma model.Materials and methods:A metastatic cervical lymph node model was created by implanting VX2 carcinoma suspension into the tongue submucosa of 21 rabbits. Computed tomography images were obtained 1, 3, 5, 10, 15 and 20 minutes after iopamidol injection, on days 11, 14, 21 (six rabbits each) and 28 (three rabbits) after carcinoma transplantation. Computed tomography lymphography was performed, and lymph node filling defects and enhancement characteristics evaluated.Results:Indirect computed tomography lymphography revealed bilateral enhancement of cervical lymph nodes in all animals, except for one animal imaged on day 28. There was significantly slower evacuation of contrast in metastatic than non-metastatic nodes. A total of 41 enhanced lymph nodes displayed an oval or round shape, or local filling defects. One lymph node with an oval shape was metastatic (one of 11, 9.1 per cent), while 21 nodes with filling defects were metastatic (21/30, 70 per cent). The sensitivity, specificity, accuracy, and positive and negative predictive values when using a filling defect diameter of 1.5 mm as a diagnostic criterion were 86.4, 78.9, 82.9, 82.6 and 83.3 per cent, respectively.Conclusion:When using indirect computed tomography lymphography to detect metastatic lymph nodes, filling defects and slow evacuation of contrast agent are important diagnostic features.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


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