Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.

Giavazzi, Raffaella; Foppolo, Marco; Dossi, Romina; Remuzzi, Andrea

doi:10.1172/jci116928

Cited by 207 publications

(171 citation statements)

References 29 publications

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“…26 In addition, soluble inflammatory mediators have been shown to increase the expression of selectin ligands on cancer cells. [27][28][29] Finally, there is emerging evidence, primarily based on in vitro studies, that a third cellular participant, the neutrophil, may contribute to inflammation-facilitated cancer cell adhesion. [30][31][32] Together, these findings suggest that states of systemic inflammation may favor the development of metastases by augmenting the recruitment of circulating tumor cells into organ tissues.…”

mentioning

confidence: 99%

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

McDonald

Spicer

Giannais

et al. 2009

Intl Journal of Cancer

204

163

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Interactions between endothelial selectins and selectin ligands expressed on tumor cells have been implicated in the binding of circulating metastatic cancer cells to the vascular endothelium during extravasation. Moreover, there is mounting evidence that inflammatory environments can accelerate the progression of metastasis by neutrophil mediated mechanisms. In this study, a physiologically relevant in vivo model of early metastasis coupled with intravital microscopy was used to visualize the trafficking of tumor cells within the liver vasculature in real time. Using GFPlabeled Lewis lung carcinoma subline H-59 cells, we show here that disrupting the interactions between endothelial selectins and tumor cell selectin ligands diminished tumor cell recruitment to the liver. Furthermore, systemic inflammation induced by intravenous injection of lipopolysaccharide significantly enhanced the metastatic potential of these lung carcinoma cells by increasing their propensity to adhere to the liver sinusoidal endothelium. Confocal microscopy revealed frequent colocalization of cancer cells with neutrophils and neutrophil depletion in vivo significantly attenuated the lipopolysaccharide-induced increase in H-59 cell adhesion. Although direct selectin-selectin ligand interactions contributed significantly to tumor cell adhesion to sinusoidal endothelial cells, we show here that in addition, interactions between adherent neutrophils within the inflamed sinusoids and circulating tumor cells may further increase tumor cell arrest in the liver. ' 2009 UICC Key words: cancer; metastasis; lung; rodent; adhesion molecules; e-selectin; neutrophil; sialyl Lewis X Lung cancer is the leading cause of cancer-related deaths worldwide. 1 A high proportion of patients harbor metastasis to regional lymph nodes upon presentation, and over half of all patients who undergo curative intent surgical resection of the lung will develop metastatic recurrence. 2 The liver is a common site of metastasis for lung cancer, with autopsy studies showing hepatic metastases in over 50% of lung cancer patients. 3 The hematogenous dissemination of cancer cells from a primary tumor to distant organs involves a cascade of sequential steps (reviewed in Refs. 4,5). The adhesion of circulating tumor cells to the vascular endothelium of distant organs is a key step in the metastatic cascade that may determine the organ tropism and extent of metastasis. Interactions between endothelial selectins and tumor cell selectin ligands have been implicated in the metastatic process. [5][6][7][8] Selectins are a family of transmembrane glycoproteins possessing an extracellular lectin domain that binds to carbohydrate moieties present on their ligands. 9 The three known selectins that function as cell adhesion molecules are expressed on the surface of endothelial cells (E-selectin and P-selectin), platelets (P-selectin) and leukocytes (L-selectin). E-selectin has been shown to contribute to the metastatic spread of multiple cancers, including lung and colon carcinoma, and m...

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mentioning

confidence: 99%

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

McDonald

Spicer

Giannais

et al. 2009

Intl Journal of Cancer

204

163

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“…Moreover, some of the cell lines express Lewis y and H type 2 antigens, indicating that secretor type A1,2FT is responsible for their synthesis. Results suggest that biosynthesis of type-1-chain tumor-associated antigens in human colon carcinoma cells is operated by secretor-type A1,2FT, as reported in normal mucosa, and that β1,3GalT activity may play a relevant role in its control.Keywords : glycosyltransferase; carbohydrate antigen; colon carcinoma ; immunostaining.Association with tumor progression and malignancy has been reported for several carbohydrate antigens [1,2] and recent data suggest this is presumably due to their involvement in selectin-dependent tumor cell adhesion to the vascular endothelium [3,4]. Type-1-chain carbohydrate antigens such as SLe a (NeuAcA2-3Galβ1-3[FucA1-4]GlcNAc) and GlcNAc) are expressed in several cancers [1, 5Ϫ8].…”

mentioning

confidence: 99%

“…Association with tumor progression and malignancy has been reported for several carbohydrate antigens [1,2] and recent data suggest this is presumably due to their involvement in selectin-dependent tumor cell adhesion to the vascular endothelium [3,4]. Type-1-chain carbohydrate antigens such as SLe a (NeuAcA2-3Galβ1-3[FucA1-4]GlcNAc) and GlcNAc) are expressed in several cancers [1, 5Ϫ8].…”

mentioning

confidence: 99%

β‐1,3‐galactosyltransferase and α‐1,2‐fucosyltransferase involved in the biosynthesis of type‐1‐chain carbohydrate antigens in human colon adenocarcinoma cell lines

Valli¹,

Gallanti²,

Bozzaro³

et al. 1998

European Journal of Biochemistry

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We studied the β-1,3-galactosyltransferase (GalT) and A-1,2-fucosyltansferase (FT) involved in the biosynthesis of type-1-chain carbohydrate antigens in human colon adenocarcinoma cell lines. We detected a GalT activity able to use GlcNAc as acceptor and found that lacto-N-biose I (Galβ1-3GlcNAc) is the only reaction product. Such β1,3GalT is kinetically similar to a pig trachea enzyme involved in mucin synthesis. The specific activity is high in cells that react strongly with anti-Lewis a and anti-Lewis b antibodies, and undetectable in a cell line that lacks antibody reaction. Reverse-transcriptase-mediated PCR analysis followed by DNA sequencing indicated that secretor-type A1,2FT is expressed in the cells, while the H type A1,2FT is not. The apparent K m values for donor and acceptor substrates determined for A1,2FT are similar to those of secretor-type A1,2FT and the specific activity measured correlates with Lewis b antigen expression on the cell surface. Moreover, some of the cell lines express Lewis y and H type 2 antigens, indicating that secretor type A1,2FT is responsible for their synthesis. Results suggest that biosynthesis of type-1-chain tumor-associated antigens in human colon carcinoma cells is operated by secretor-type A1,2FT, as reported in normal mucosa, and that β1,3GalT activity may play a relevant role in its control.Keywords : glycosyltransferase; carbohydrate antigen; colon carcinoma ; immunostaining.Association with tumor progression and malignancy has been reported for several carbohydrate antigens [1,2] and recent data suggest this is presumably due to their involvement in selectin-dependent tumor cell adhesion to the vascular endothelium [3,4]. Type-1-chain carbohydrate antigens such as SLe a (NeuAcA2-3Galβ1-3[FucA1-4]GlcNAc) and GlcNAc) are expressed in several cancers [1, 5Ϫ8]. Specific involvement of SLe a in selectin-dependent cell adhesion has been suggested [9, 10] and its stage-specific expression has been described in embryonic pancreas [11]. In the case of Le b, as well as in that of its type 2 chain counterpart Le y (FucA1-2Galβ1-4[FucA1-3]GlcNAc) [12,13], the molecular basis of their association with malignancy is still not fully elucidated.The biosynthesis of type-1-chain tumor markers depends on the activity of a galactosyltransferase (GalT) able to operate the Correspondence to

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“…Only a small proportion of their experiments pertained to OVCAR3 cells, but results showed that little interaction occurred between the resting HUVEC surface layer and OVCAR3 cells, while minimal attachment and rolling occurred on IL-1 activated HUVECs. 55 These findings implicate that specific adhesion mechanisms are necessary for ovarian tumor cell attachment and extravasation, while the cell type also plays a critical role in which attachment or rolling mechanisms are utilized. A compact summary of the shear stress mechanotransduction studies on ovarian cancer is detailed in Table I with schematics of select bioreactors shown in Fig.…”

Section: B Shear Stress Models Specific To Ovarian Cancermentioning

confidence: 87%

“…The spread of ovarian cancer to distant metastatic sites through tumor cells that have intravasated to the circulation and then extravasate and colonize a new tumor site was investigated by Egan et al 54 and Giavazzi et al 55 Egan et al utilized a simple cone and plate viscometer setup to test the protection potential of platelets when sheared under venous and arterial stresses with A2780 (endometrioid histotype) ovarian cancer cells. This setup was designed to test the viability of circulating tumor cells under physiological shear stresses within arterial and venous circulation.…”

Section: B Shear Stress Models Specific To Ovarian Cancermentioning

confidence: 99%

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

2018

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Perspective: The role of mechanobiology in the etiology of brain metastasis APL Bioengineering 2, 031801 (2018) Ovarian cancer remains a deadly diagnosis with an 85% recurrence rate and a 5-year survival rate of only 46%. The poor outlook of this disease has improved little over the past 50 years owing to the lack of early detection, chemoresistance and the complex tumor microenvironment. Within the peritoneal cavity, the presence of ascites stimulates ovarian tumors with shear stresses. The stiff environment found within the tumor extracellular matrix and the peritoneal membrane are also implicated in the metastatic potential and epithelial to mesenchymal transition (EMT) of ovarian cancer. Though these mechanical cues remain highly relevant to the understanding and treatment of ovarian cancers, our current knowledge of their biological processes and their clinical relevance is deeply lacking. Seminal studies on ovarian cancer mechanotransduction have demonstrated close ties between mechanotransduction and ovarian cancer chemoresistance, EMT, enhanced cancer stem cell populations, and metastasis. This review summarizes our current understanding of ovarian cancer mechanotransduction and the gaps in knowledge that exist. Future investigations on ovarian cancer mechanotransduction will greatly improve clinical outcomes via systematic studies that determine shear stress magnitude and its influence on ovarian cancer progression, metastasis, and treatment.

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Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.

Cited by 207 publications

References 29 publications

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

β‐1,3‐galactosyltransferase and α‐1,2‐fucosyltransferase involved in the biosynthesis of type‐1‐chain carbohydrate antigens in human colon adenocarcinoma cell lines

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

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