Clinical patterns of metastasis

Leong, Stanley P. L.; Cady, Blake; Jablons, David M.; Garcia‐Aguilar, Julio; Reintgen, Douglas S.; Jakub, James W.; Pendas, Solange; Duhaime, Lisa; Cassell, Robert; Gardner, Mary; Giuliano, Rosemary; Archie, Victor C.; Calvin, Douglas P.; Mensha, L.; Shivers, Steven C.; Cox, Charles E.; Werner, Jochen A.; Kitagawa, Yuko; Kitajima, Masaki

doi:10.1007/s10555-006-8502-8

Cited by 116 publications

(85 citation statements)

References 110 publications

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“…Blindending lymphatic capillaries drain fluid, cells, and macromolecules from tissue interstitium into a hierarchy of vessels punctuated by lymph nodes (LN), which provide immunologic surveillance for a particular lymphatic drainage basin (3). The presence of metastatic tumor cells in the "sentinel" LN draining a tumor site is a key factor in disease management: substantial clinical data indicates adverse prognostic significance of tumor-positive LNs for many tumor types (4,5). However, a clear understanding of the mechanistic role of LNs in tumor progression is still lacking.…”

Section: Introductionmentioning

confidence: 99%

A Role for Bone Morphogenetic Protein-4 in Lymph Node Vascular Remodeling and Primary Tumor Growth

et al. 2011

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Lymph node metastasis, an early and prognostically important event in the progression of many human cancers, is associated with expression of VEGF-D. Changes to lymph node vasculature that occur during malignant progression may create a metastatic niche capable of attracting and supporting tumor cells. In this study, we sought to characterize molecules expressed in lymph node endothelium that could represent therapeutic or prognostic targets. Differential mRNA expression profiling of endothelial cells from lymph nodes that drained metastatic or nonmetastatic primary tumors revealed genes associated with tumor progression, in particular bone morphogenetic protein-4 (BMP-4). Metastasis driven by VEGF-D was associated with reduced BMP-4 expression in high endothelial venules, where BMP-4 loss could remodel the typical high-walled phenotype to thin-walled vessels. VEGF-D expression was sufficient to suppress proliferation of the more typical BMP-4-expressing high endothelial venules in favor of remodeled vessels, and mechanistic studies indicated that VEGF receptor-2 contributed to high endothelial venule proliferation and remodeling. BMP-4 could regulate high endothelial venule phenotype and cellular function, thereby determining morphology and proliferation responses. Notably, therapeutic administration of BMP-4 suppressed primary tumor growth, acting both at the level of tumor cells and tumor stromal cells. Together, our results show that VEGF-D-driven metastasis induces vascular remodeling in lymph nodes. Furthermore, they implicate BMP-4 as a negative regulator of this process, suggesting its potential utility as a prognostic marker or antitumor agent. Cancer Res; 71(20); 6547-57. Ó2011 AACR.

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Section: Introductionmentioning

confidence: 99%

A Role for Bone Morphogenetic Protein-4 in Lymph Node Vascular Remodeling and Primary Tumor Growth

et al. 2011

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“…Although malignant cancers can spread to a wide variety of body tissues, only a few tissues, such as lymph nodes, bone, liver and lung, offer favorable conditions for metastasized cancer cell survival [4] . It has recently been suggested that the chemokine and chemokine receptor family [1] play a significant role in this organ tropism.…”

Section: Introductionmentioning

confidence: 99%

Topotecan inhibits cancer cell migration by down-regulation of chemokine CC motif receptor 7 and matrix metalloproteinases

et al. 2009

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Aim:The aim of this study was to investigate the effect of topotecan (TPT) on cancer cell migration. Methods: Growth inhibition of TPT was analyzed by MTT assay, and cancer cell migration was measured by transwell double chamber assay. To verify the effect of TPT on the chemokine receptors CXCR4 and CCR7, quantitative PCR, semiquantitative PCR and Western blot analysis were performed. The secretion of MMP-2 and MMP-9 was detected by enzymelinked immunosorbent assay (ELISA) and gelatin zymography. To evaluate possible contributions of CCR7 to MMP secretion, the overexpression vectors pcDNA3.1 + -CCR7 and CCR7 siRNA were transiently transfected into MDA-MB-435 cells. Results: TPT inhibited cancer cell migration in a dose-dependent manner. Additionally, TPT significantly decreased the expression of CCR7 in both MDA-MB-435 and MDA-MB-231 cells and moderately reduced the expression of CXCR4 in MDA-MB-435 cells. The secretion of MMPs (MMP-2, MMP-9) was also inhibited by TPT. Overexpression of CCR7 increased the secretion of MMP-2/9 and cancer cell migration, whereas knockdown of CCR7 reduced active MMP-2/9 production and migration of MDA-MB-435 cells. Conclusion: TPT inhibited cancer cell migration by down-regulation of CCR7 and MMPs (MMP-2 and MMP-9).

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“…PET together with CT images showed a 15% increase in the accurate identification of nodal staging over using the PET images alone (Jeong, et al, 2007). PET/CT seems to have a higher sensitivity and specificity for detecting lymph node metastasis (Leong, et al, 2006, Wild, et al, 2006.…”

Section: Positron Emssion Tomography (Pet)mentioning

confidence: 93%