Prevention of tumor metastasis formation by anti-variant CD44.

A splice variant of CD44 (CD44v) originally discovered on metastases of a rat pancreatic adenocarcinoma (BSp73ASML) has been shown by transfection to confer metastatic behavior to nonmetastatic tumor cells (Günthert U., M. Hofmann, W. Rudy, S. Reber, M. Zöller, I. Haussmann, S. Matzku, A. Wenzel, H. Ponta, and P. Herrlich. 1991. Cell. 65:13). A monoclonal antibody (mAb), 1.1ASML, to the metastasis-specific domain of the CD44v molecule retards growth of lymph node and lung metastases of the metastatic tumor line BSp73ASML, and can efficiently prevent formation of metastases by the transfected line. The antibody is only effective when given before lymph node colonization. Anti-CD44v does not downregulate the expression of CD44v, and prevention of metastatic growth by anti-CD44v is not due to activation of any kind of immune defense. We suggest that the mAb interferes with proliferation of metastasizing tumor cells in the draining lymph node, most probably by blocking a ligand interaction. The interference with metastatic spread will greatly facilitate the exploration of the function of CD44v and, in particular, may also open new strategies for the therapy of human metastases.

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Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.

Journal of Experimental Medicine ◽

10.1084/jem.154.2.253 ◽

1981 ◽

Vol 154 (2) ◽

pp. 253-261 ◽

Cited By ~ 4

Author(s):

J T Hunter ◽

M P Ashley ◽

S Sukumar ◽

T Sugimoto ◽

B Zbar ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Tumor Cells ◽

Guinea Pigs ◽

Lung Metastases ◽

Stage Ii ◽

Water Emulsion ◽

Experimental Cancer ◽

Limited Surgery ◽

Draining Lymph Node

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.

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Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Cancers ◽

10.3390/cancers12123798 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3798

Author(s):

Stephanie Annett ◽

Gillian Moore ◽

Tracy Robson

Keyword(s):

Adipose Tissue ◽

Tumor Microenvironment ◽

Tumor Cells ◽

Cancer Metastasis ◽

Metastatic Tumor ◽

Established Risk Factor ◽

Metastatic Behavior ◽

Obesity And Cancer ◽

Enhance Tumor Growth

Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity–metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor–adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.

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Peri-operative imaging techniques of the sentinel lymph node in veterinary oncology

Vlaams Diergeneeskundig Tijdschrift ◽

10.21825/vdt.v90i3.20406 ◽

2021 ◽

Vol 90 (3) ◽

pp. 115-124

Author(s):

P. De Bie ◽

S. Favril ◽

S. De Vos ◽

H. De Rooster

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Tumor Cells ◽

Imaging Techniques ◽

Lymphatic Vessels ◽

Metastatic Tumor ◽

Mapping Technique ◽

Distant Metastatic Disease ◽

Metastatic Cells ◽

Lymphatic Pathway

When cancer cells spread through lymphatic vessels, the first lymph node they reach is the sentinel lymph node (SLN). Hence, if the SLN is free from metastatic cells, it can be assumed that further lymph nodes will be free of metastatic tumor cells too. If metastatic tumor cells are identified in the SLN, the patient is at risk of developing distant metastatic disease. In that case, further diagnostic and therapeutic steps are needed and the patient’s prognosis gets worse. The SLN can be located at an anatomically unpredictable location. This is likely due to lymphangiogenesis, which alters the normal lymphatic pathway and drains the metastatic cells to another lymph node than the expected anatomically closest one. Therefore, identifying the SLN by an accurate mapping technique is necessary. In this article, the existing techniques for SLN mapping are reviewed, and their use in human and veterinary medicine is compared.

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Adoptive Cellular Therapy With Tumor Vaccine Draining Lymph Node Lymphocytes After Vaccination With HLA-B7/β2-Microglobulin Gene-Modified Autologous Tumor Cells

Journal of Immunotherapy ◽

10.1097/00002371-200207000-00008 ◽

2002 ◽

Vol 25 (4) ◽

pp. 359-372 ◽

Cited By ~ 22

Author(s):

Sybren L. Meijer ◽

Annemieke Dols ◽

Walter J. Urba ◽

Hong-Ming Hu ◽

John W. Smith ◽

...

Keyword(s):

Lymph Node ◽

Tumor Cells ◽

Cellular Therapy ◽

Tumor Vaccine ◽

Autologous Tumor ◽

Adoptive Cellular Therapy ◽

Β2 Microglobulin ◽

Draining Lymph Node

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Interleukin 4 controls the role of macrophages in pulmonary metastatic tumor cell seeding and growth

10.1101/2021.12.28.474388 ◽

2021 ◽

Author(s):

Carolina A Rodriguez-Tirado ◽

David Entenberg ◽

Jiufeng Li ◽

Bin-Zhi Qian ◽

John S Condeelis ◽

...

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Lung Metastasis ◽

Lung Metastases ◽

Macrophage Polarization ◽

Metastatic Tumor ◽

Interferon Γ ◽

Interleukin 4 ◽

Physical Interaction

Metastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival, and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected trans-endothelial migration of tumor cells in vitro. Interferon γ and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα) null mice develop fewer and smaller lung metastasis. Adoptive transfer of wild type monocytes to IL4rα deficient mice rescued this phenotype. IL4 signaling in macrophages controls the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages transcriptionally regulates several other genes already causally associated with lung metastasis including CCL2, CSF1, CCR1, HGF and FLT1. The central role for IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages. This interaction enhances tumor cell survival. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages.

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MHC Class 1 and PDL-1 Status of Primary Tumor and Lymph Node Metastatic Tumor Tissue in Gastric Cancers

Gastroenterology Research and Practice ◽

10.1155/2019/4785098 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Ibrahim Halil Erdogdu

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Cancer Cells ◽

Tumor Cells ◽

Primary Tumor ◽

Tumor Tissue ◽

Metastatic Tumor ◽

Tumor Escape ◽

Metastatic Tumors ◽

Primary Tumors

The prognosis of metastatic gastric cancer is poor. Despite the use of VEGF-, EGFR-, and HER2-targeting agents, prognosis is still poor in advanced gastric cancer. Although cancer immunotherapy responds well in some patients, clinical use is limited due to unanswered patients. For this reason, it is necessary to know the characteristics of primary and metastatic cancer cells for patient selection for immunotherapy and additional criteria are required. MHC-1 downregulation is most frequently observed in the tumor escape mechanism of cancer cells from the immune system. MHC-1 downregulation with increased PDL-1 expression of cancer cells has an important role in immune escape. MHC-1 downregulation and PDL-1 expression have been shown in many types of cancers. However, there is no study on the status of MHC-1 and PDL-1 in primary and metastatic tumor tissue. In this study, MHC-1 and PDL-1 score in primary and metastatic tumor cells was evaluated in 43 gastric cancer patients with lymph node metastasis. According to our results, the primary tumor PDL-1 score was correlated with the number of metastatic lymph nodes (r=0.258; p=0.024) and primary tumor size (r=0.341; p=0.045). A similar correlation was found between the primary tumor PDL-1 score and the metastatic tumor PDL-1 score (r=0.213; p=0.015). In our study, MHC-1 was found to be higher in primary tumors than metastatic tumors, although not statistically significant (p=0.054). The results of our study showed high MHC-1 and low PDL-1 expression in primary tumors and low MHC-1 and high PDL-1 expression in metastatic tumors. These results reveal different biological characteristics of primary and metastatic tumor cells.

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