Tumor-Microenvironment Interactions

Zipin, Adi; Israeli-Amit, Mira; Meshel, Tsipi; Sagi‐Assif, Orit; Yron, Ilana; Lifshitz, Veronica; Bacharach, Eran; Smorodinsky, Nechama I.; Many, Ariel; Czernilofsky, Peter A.; Morton, Donald L.; Witz, Isaac P.

doi:10.1158/0008-5472.can-03-4038

Cited by 52 publications

(15 citation statements)

References 39 publications

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“…Each glass slide was treated with a fibronectin solution of 20μg/ml [56]. 270.000 HUVEC cells were suspended in 2 ml of EMB medium (Lonza), plated on each well and left o/n at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Humanα-L-fucosidase-1attenuates the invasive properties of thyroid cancer

et al. 2017

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Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.

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“…Each glass slide was treated with a fibronectin solution of 20μg/ml [56]. 270.000 HUVEC cells were suspended in 2 ml of EMB medium (Lonza), plated on each well and left o/n at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Humanα-L-fucosidase-1attenuates the invasive properties of thyroid cancer

et al. 2017

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“…Most of our understanding of intracellular signaling has been gained in the analysis of transiently activated pathways as normally observed Also tumors do not function as isolated entities but have multiple signaling exchanges with the tumor environment. The interaction of cancer cells with other cells and/or components like the extracellular matrix of the microenvironment contribute to the survival and proliferation of tumor cells [55,56]. Therefore, pharmacological disruption of these interactions also represents a novel and increasingly important avenue for treatment of cancer and in particular of metastatic spread.…”

Section: Inhibition Of Intracellular Signaling For Therapeutic Purposmentioning

confidence: 99%

Signaling Through RAS-RAF-MEK-ERK: from Basics to Bedside

Zebisch¹,

Czernilofsky²,

Kéri³

et al. 2007

CMC

105

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Aberrant signaling caused by mutations in the RAS-RAF-MEK-ERK pathway and its upstream activators critically contributes to human tumor development. Strategies, which aim at inhibiting hyperactive signaling molecules, appear conceptually straight forward, but their translation into clinical practice has been hampered by many setbacks. Understanding structure, function and regulation of this intracellular pathway as well as its crosstalk with other signaling activities in the cell will be essential to ensure reasonable usage of new therapeutic possibilities. This review provides an understanding of this signaling cascade as revealed by genetic and biochemical approaches and discusses the existing or arising possibilities to interfere with unphysiological activation in cancer. Signaling aberrations and signal transduction therapies will be discussed exemplary for two types of hematological neoplasia, acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). In the future understanding the role of tumor stem cells, both as a source of tumor recurrence and tumor heterogeneity, the signals controlling their fate as well as epigenetic changes in cancer will be the next critical steps to further advance the applicability of these novel therapeutic strategies.

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“…In contrast, our own group [6] and other authors [7] demonstrated specific tumor cell adhesion in the microcirculation of the liver and lung [8,9]. Furthermore, injected human colon cancer cells showed an organ specific pattern of cell adhesion in rats, mimicking the clinical picture of metastatic colon cancer [10].…”

Section: Introductionmentioning

confidence: 95%

“…Obviously, malignant cells originating from a variety of tissues differ with regard to available adhesion molecules for cell - cell or cell - ECM interactions. For example, E-Selectin mediated adhesion to endothelial cells has been established for inflammatory leucocytes as well as several human cancer cells [7-9]…”

Section: Introductionmentioning

confidence: 99%

In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

et al. 2010

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BackgroundMetastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer.MethodsAnaesthetized CD rats were mechanically ventilated and 106 human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection.ResultsAfter vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p < 0.05). The same degree of impairment was achieved by inhibition of P- and L-selectins via animal treatment with fucoidan (p < 0.05) and also by inhibition of the Thomson-Friedenreich (TF)-antigen (p < 0.05).ConclusionsThese results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.

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Tumor-Microenvironment Interactions

Cited by 52 publications

References 39 publications

Humanα-L-fucosidase-1attenuates the invasive properties of thyroid cancer

Humanα-L-fucosidase-1attenuates the invasive properties of thyroid cancer

Signaling Through RAS-RAF-MEK-ERK: from Basics to Bedside

In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

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