Characterization of Human Colon Carcinoma Variant Cells Selected for Sialyl Lex Carbohydrate Antigen: Liver Colonization and Adhesion to Vascular Endothelial Cells

Izumi, Yuki; Taniuchi, Yuta; Tsuji, Tsutomu; Smith, C. Wayne; Nakamori, Shoji; Fidler, Isaiah J.; Irimura, Tatsuro

doi:10.1006/excr.1995.1027

Cited by 122 publications

(73 citation statements)

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“…The incidence of liver recurrence was significantly higher in SLXpositive patients than in SLX-negative ones (P = 0.028). These results were consistent with the results of previous animal and in vitro reports, which stated that SLX was a ligand carbohydrate of selection and played an important role during haematogenous metastasis (Saitoh et al, 1992;Sawada et al, 1992;Takada et al, 1993;Izumi et al, 1995;Bresalier et al, 1996). The present study revealed that the frequencies of SLX positivity, synchronous liver metastasis and liver recurrence were significantly higher with differentiated carcinoma than with undifferentiated carcinoma (P < 0.0001, P = 0.021 and P = 0.028, respectively).…”

Section: Discussionsupporting

confidence: 93%

“…In vitro study showed that these carbohydrates were involved in the adhesion of tumour cells from gastric carcinoma, colon carcinoma, hepatoma, pancreatic carcinoma and lung carcinoma to E-selectin, which is present on cytokine-activated human endothelial cells (Takada et al, 1993). It was also reported that colon carcinoma cells which were highly metastatic to the liver expressed relatively more SLX structures than their corresponding low metastatic counterparts, and that the increased expression of SLX correlated with strong adherence to vascular endothelial cells with E-selectin (Saitoh et al, 1992;Sawada et al, 1992;Izumi et al, 1995;Bresalier et al, 1996). These findings suggest that SLX play important roles during haematogeneous tumour metastasis.…”

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confidence: 94%

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Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

et al. 2000

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SummarySialyl Lewis x antigen (SLX) is a carbohydrate antigen that serves as a ligand for selectin, an adhesion molecule expressed on vascular endothelial cells. The expression of SLX in 245 patients with advanced gastric carcinoma was examined immunohistochemically, and its clinicopathologic significance was analysed. We classified the patients with advanced gastric carcinoma into 91 with differentiated type and 154 with undifferentiated type. SLX expressed in 135 of 245 patients (55%), comprising 68 (75%) patients with differentiated carcinoma and 67 (44%) with undifferentiated carcinoma. The positive rate for SLX expression was significantly higher among patients with differentiated carcinoma than among those in undifferentiated carcinoma (P < 0.0001). With differentiated carcinoma, the incidence of lymph node metastasis, advanced tumour stage (stage III and IV) and liver recurrence was significantly higher in SLX-positive patients than in SLXnegative ones (P < 0.0001, P = 0.0065 and P = 0.028, respectively). Moreover, the prognoses were better in patients with SLX-negative tumours than in those with SLX-positive tumours (P = 0.019). With undifferentiated carcinoma, there were no significant correlations between SLX expression and any clinicopathological features or prognoses. The clinicopathologic significance of SLX expression in gastric carcinoma patients depends on histologic type. SLX expression may be of great relevance in predicting liver metastases in patients with differentiated carcinoma.

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Section: Discussionsupporting

confidence: 93%

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confidence: 94%

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

et al. 2000

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“…E-, P-, and L-selectins are vascular receptors for certain normal sialyl Lewis x/a containing mucin-type glycoproteins found on leukocytes and endothelium (40)(41)(42)(43). Because selectins can mediate tumor cell interactions with platelets, leukocytes, and endothelium in vitro (39,44,45), an in vivo role for selectins in the metastatic spread of tumors has been suggested (31,33,34). P-selectin expressed on activated endothelium contributes to the rolling of leukocytes that can result in their arrest and extravasation.…”

Section: Biochemistry For the Article ''Functional Transitions In Mymentioning

confidence: 99%

Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis

Borsig

Wong

Feramisco

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

623

650

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Independent studies indicate that expression of sialylated fucosylated mucins by human carcinomas portends a poor prognosis because of enhanced metastatic spread of tumor cells, that carcinoma metastasis in mice is facilitated by formation of tumor cell complexes with blood platelets, and that metastasis can be attenuated by a background of P-selectin deficiency or by treatment with heparin. The effects of heparin are not primarily due to its anticoagulant action. Other explanations have been suggested but not proven. Here, we bring together all these unexplained and seemingly disparate observations, showing that heparin treatment attenuates tumor metastasis in mice by inhibiting P-selectin-mediated interactions of platelets with carcinoma cell-surface mucin ligands. Selective removal of tumor mucin P-selectin ligands, a single heparin dose, or a background of P-selectin deficiency each reduces tumor cell-platelet interactions in vitro and in vivo . Although each of these maneuvers reduced the in vivo interactions for only a few hours, all markedly reduce long-term organ colonization by tumor cells. Three-dimensional reconstructions by using volume-rendering software show that each situation interferes with formation of the platelet “cloak” around tumor cells while permitting an increased interaction of monocytes (macrophage precursors) with the malignant cells. Finally, we show that human P-selectin is even more sensitive to heparin than mouse P-selectin, giving significant inhibition at concentrations that are in the clinically acceptable range. We suggest that heparin therapy for metastasis prevention in humans be revisited, with these mechanistic paradigms in mind.

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“…14 Numerous groups have reported a correlation between increased expression of sLe x on tumor cells and higher rates of metastasis and poor prognosis. 49 Clinical studies of colon cancer progression have suggested that the percentage of sLe x expressing cells within the primary tumors and the degree of sialylation are prognostic indicators of tumor aggressiveness. 14,15 Furthermore, Zipin et al 16 reported that reducing the surface expression of fucosylated sLe x on tumor cells attenuated their capacity to adhere to E-selectin.…”

Section: Discussionmentioning

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

201

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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Characterization of Human Colon Carcinoma Variant Cells Selected for Sialyl Lex Carbohydrate Antigen: Liver Colonization and Adhesion to Vascular Endothelial Cells

Cited by 122 publications

References 0 publications

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis

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

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