Preclinical Models of Regional Lymph Node Tumor Metastasis

Nathanson, S. David

doi:10.1007/978-0-387-69219-7_10

Cited by 8 publications

(15 citation statements)

References 126 publications

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“…1,4,10 Extensive work in the metastatic cascade yielded much information about the key steps in the process. 1,18 Tumor cells invade breast parenchymal tissue, a process requiring proteolysis, adhesion receptors, and directional motility, but little is known about the initial steps whereby the cells interact with tumoral or peritumoral vessels and gain access to the systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

“…9 Preclinical and clinical studies of RLN metastasis and identification of LVI using specific immunohistochemical stains that distinguish lymphatic endothelial cells (LECs) from blood vessel endothelial cells (BECs) strongly suggest that lymphatic invasion is the preferred method by which tumor cells metastasize to the RLNs, but fail to also conclude that this initial lymphatic invasion is also the predominant method by which tumor cells gain access to the systemic circulation. [10][11][12][13] We interrogated our breast cancer sentinel lymph node (SLN) database, providing a 14-year follow-up of our patients, to determine whether the relationships among LVI, RLN, and systemic metastases support direct peritumoral and/or intratumoral BVC or LC invasion as the predominant pattern of metastasis.…”

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confidence: 99%

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The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Nathanson

Kwon

Kapke

et al. 2010

Indian J Surg Oncol

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BACKGROUND.: Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. METHODS.: Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. RESULTS.: Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P < .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (< .0001). Patients with LVI/HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative. Systemic metastasis was significantly (P = .0013) associated with LVI/ RLN positive, but not with LVI positive/RLN negative patients (P = .137). CONCLUSIONS.: LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Nathanson

Kwon

Kapke

et al. 2010

Indian J Surg Oncol

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“…The procedure includes the search for single or small clusters of cancer cells by immunohistochemistry with antibodies that do not recognize host cells [104]. Transgenic animals manipulated genetically to produce lymph node metastasis are reviewed by Nathanson [67]. Experimental and clinical analysis emphasizes the role of the chemokines and their receptors that were first described for the homing of leukocytes [105].…”

Section: Lymph Node Metastasismentioning

confidence: 99%

“…In inflammatory breast cancer, which is associated with regional lymph node metastasis in most cases, there are a higher number of lymph vessels than in the noninflammatory counterparts, suggesting a contribution of lymph angiogenesis to nodal spread. In most experimental models, peritumoral lymphangiogensis is a prerequisite for metastasis to regional lymph nodes [67].…”

Section: Endothelial Cellsmentioning

confidence: 99%

“…Both processes are considered to be active, implicating chemotactic migration [121]. At least for lymphatics, passive intravasation should not be excluded [67]. Lack of a functional intratumoral lymphatic network, neoangiogenesis, and increased permeability of new blood vessels create interstitial hypertension and an increased centrifugal lymphatic flow.…”

Section: The Invasion Programmentioning

confidence: 99%

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Cancer invasion and metastasis: interacting ecosystems

2009

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Malignant tumors invade and metastasize. They consist of cancer cells, evolving through genetic and epigenetic modulation, mixed with tumor-associated host cells, emerging from resident or bone marrow-derived precursors. These cells establish ecosystems to activate cellular programs for local invasion and distant metastasis. Characteristic of such malignancy-related activities is communication inside ecosystems between cells, ligands, receptor protein complexes, and signaling pathways as well as between ecosystems comprising the primary tumor, lymph node and distant metastasis, bone marrow and blood and lymph circulation. Complexity is another characteristic, resulting from: heterogeneity of the cell populations; the numbers of promoter and suppressor genes, their levels of regulation, and the pleiotropic activities of their products; biological redundancy of the molecular mechanisms underpinning invasion-related activities. Clinical attention is paid to putative new targets, namely host cells, individual molecules and their signaling pathways, as well as the effects of current treatment on invasion and metastasis.

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