Expression of L-selectin and efficient binding to high endothelial venules do not modulate the dissemination potential of murine B-cell lymphoma

Aviram, Ronit; Raz, Nava; Kukulansky, T.; Hollander, Nurit

doi:10.1007/pl00006682

Cited by 7 publications

(14 citation statements)

References 25 publications

(49 reference statements)

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“…It has been demonstrated by Jonas et al (27) that 38C-13 cells, in contrast to resting lymphocytes, reach the lymph nodes by an L-selectin-independent mechanism. In agreement with their data, we have recently reported that L-selectin is not required for lymph node metastasis of 38C-13, as anti-L-selectin did not inhibit tumor dissemination to peripheral lymph nodes, and L-selectinnegative 38C-13 variant cells disseminated as efficiently as wildtype cells (21). Here we demonstrate that the bispecific Ab reduced the migration rate of 38C-13 cells into lymph nodes, which correlates with its inhibitory effect on lymph node metastasis.…”

Section: Discussionsupporting

confidence: 91%

“…Tumor dissemination was determined by cell proliferation assays as previously described (21). Briefly, lymph node, spleen, and hepatic single-cell suspensions were incubated for 24 h at 1 ϫ 10 5 cells/well in flat-bottom 96-well microplates.…”

Section: Determination Of Tumor Metastasismentioning

confidence: 99%

“…into mice, they grow at the site of inoculation and disseminate to different organs, including lymph nodes, spleen, lung, liver, and bone marrow (20,21). Tumor dissemination is manifested by enlargement of the infiltrated organs, as determined by increases in organ weight and cell number.…”

Section: Anti-id ϫ Anti-lfa-1 Bispecific Abs Inhibit Metastasis Of 38mentioning

confidence: 99%

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Anti-idiotype × Anti-LFA-1 Bispecific Antibodies Inhibit Metastasis of B Cell Lymphoma

Cohen

Haimovich

Hollander

2003

The Journal of Immunology

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Abs to adhesion molecules can block tumor metastasis. However, they may also block the function of normal cells. To circumvent this adverse effect, we proposed the use of bispecific Abs that bind simultaneously to an adhesion receptor and to a tumor-specific Ag. Such Abs bind more avidly to tumor cells that coexpress both target Ags than to normal cells. The Id of the surface Ig of malignant B lymphocytes is a tumor-specific Ag. We therefore produced a bispecific Ab with specificity to the adhesion molecule LFA-1 and to the Id of the murine B cell lymphoma 38C-13. Here we demonstrate that this Ab blocked liver metastasis in mice carrying primary s.c. tumors and partially inhibited lymph node metastasis. Migration of 38C-13 cells to liver and lymph nodes was inhibited by the bispecific Ab, while migration to spleen was not affected. Hence, the bispecific Ab-mediated reduction in liver and lymph node metastasis resulted at least in part from reduced homing to these organs. In contrast to anti-LFA-1 monospecific Abs, the anti-Id × anti-LFA-1 bispecific Ab did not affect immune responses such as delayed-type hypersensitivity. Hence, bispecific Abs against adhesion molecules and against tumor-specific Ags may selectively block tumor metastasis in a way that may leave much of the immune system intact.

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Section: Discussionsupporting

confidence: 91%

Section: Determination Of Tumor Metastasismentioning

confidence: 99%

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Anti-idiotype × Anti-LFA-1 Bispecific Antibodies Inhibit Metastasis of B Cell Lymphoma

Cohen

Haimovich

Hollander

2003

The Journal of Immunology

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“…Tumor dissemination was determined by cell proliferation assays as described (30). Briefly, lymph node, spleen, and bone marrow single-cell suspensions were incubated for 24 h at 1 ϫ 10 5 cells per well in 96-well flat-bottom microplates.…”

Section: Determination Of Tumor Metastasismentioning

confidence: 99%

Anti-Idiotype × Anti-CD44 Bispecific Antibodies Inhibit Invasion of Lymphoid Organs by B Cell Lymphoma

Avin

Haimovich

Hollander

2004

The Journal of Immunology

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The demonstration that Abs to adhesion molecules can block tumor metastasis suggested their use for therapy. However, such Abs affect nonmalignant cells as well. To circumvent this adverse effect, we proposed the use of bispecific Abs that bind simultaneously to an adhesion receptor and to a tumor-specific Ag. Such bifunctional Abs bind more avidly to tumor cells that coexpress both target Ags than to normal cells. The Id of the surface Ig of malignant B lymphocytes is a tumor-specific Ag. Therefore, we produced bispecific Abs with specificity to the adhesion molecule, CD44, and to an idiotypic determinant of the murine B cell lymphoma, 38C-13. These anti-Id × anti-CD44 bispecific Abs blocked 38C-13 cell adhesion to hyaluronic acid, while not affecting adhesion of Id-negative cells. In vivo studies demonstrated that the bispecific Abs inhibited lymphoma cell dissemination to the lymph nodes, bone marrow, and spleen, and prolonged survival of tumor-bearing mice. Migration of 38C-13 cells to the lymphoid organs was inhibited by the bispecific Abs. Thus, the bispecific Ab-mediated reduction in metastasis resulted, at least in part, from reduced homing to these organs. In contrast to anti-CD44 monospecific Abs, the anti-Id × anti-CD44 bispecific Abs did not affect immune responses such as delayed-type hypersensitivity. Hence, bispecific Abs against adhesion molecules and tumor-specific Ags may selectively block tumor metastasis in a way which may leave at least part of the immune system intact.

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“…Transgenic ectopic expression of L-selectin in a spontaneous mouse carcinoma model facilitated lymph node metastasis (37). However, naturally occurring L-selectin on a B cell lymphoma cell line was not associated with enhanced lymph node metastasis (38). Regardless, in contrast to P-and E-selectin, there has been no documented role for normal leukocyte L-selectin in facilitating the metastasis of adenocarcinomas.…”

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confidence: 99%

Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis

Borsig

Wong

Hynes

et al. 2002

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

366

398

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Here we show similar findings with a murine adenocarcinoma in syngeneic immunocompetent mice but involving a different P-selectin ligand, possibly a sulfated glycolipid. Thus, metastatic spread can be facilitated by tumor cell selectin ligands other than mucins. Surprisingly, L-selectin expressed on endogenous leukocytes also facilitates metastasis in both the syngeneic and xenogeneic (T and B lymphocyte deficient) systems. PL-selectin double deficient mice show that the two selectins work synergistically. Although heparin can block both P-and L-selectin in vitro, the in vivo effect of a single heparin dose given before tumor cells seems to be completely accounted for by blockade of P-selectin function. Thus, L-selectin on neutrophils, monocytes, and͞or NK cells has a role in facilitating metastasis, acting beyond the early time points wherein P-selectin mediates interactions of platelet with tumor cells.cancer ͉ heparin ͉ glycolipids ͉ platelets H ematogeneous metastasis occurs when tumor cells enter the bloodstream, interact with host blood cells, and eventually colonize a distant tissue. Much evidence indicates that hematogenously disseminating tumor cells interact with platelets and leukocytes, forming microemboli that facilitate their arrest in the vasculature (1-4). Although the contribution of platelets to metastasis has been confirmed in several experimental settings (1, 2, 5-10), the mechanisms and significance of leukocyte participation in tumor microemboli remain largely unknown.Altered cell surface glycosylation is a prominent feature of tumor cells (11)(12)(13)(14)(15). In particular, the expression of sialylated fucosylated glycans like sialyl Lewis x/a correlate with a poor prognosis because of tumor progression and a high rate of metastasis (for examples, see refs. 16-18). Selectins are vascular cell adhesion molecules that recognize certain sialyl Lewis x/a carrying mucin-type glycoproteins found on normal leukocytes and endothelium (11,(19)(20)(21)(22)(23). Carcinoma cell surface molecules carrying sialyl Lewis x/a also can be recognized by all three selectins (11-15, 17, 24-27), mediating tumor cell interactions with platelets, leukocytes, and endothelium in vitro (10,25,27,28). Based on such data, an in vivo role for E-and P-selectins in metastatic spread has been suggested. The hypothesis that E-selectin on activated endothelium might facilitate cancer cell seeding (14, 29) is supported by transgenic over-expression of E-selectin in the mouse liver, which redirected metastases to this organ (30), and a system where tumor cell expression of sialylated fucosylated glycans was increased by transfecting a fucosyltransferase (31). Carcinoma lines expressing E-selectin ligands also displayed an increased metastatic capacity in cytokine-pretreated mice (32). However, E-selectin is not constitutively expressed in vivo but must be transcriptionally activated by certain stimuli. We have previously shown that platelets adhere to some human carcinoma cells mostly via P-selectin and that inhibition of th...

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Expression of L-selectin and efficient binding to high endothelial venules do not modulate the dissemination potential of murine B-cell lymphoma

Cited by 7 publications

References 25 publications

Anti-idiotype × Anti-LFA-1 Bispecific Antibodies Inhibit Metastasis of B Cell Lymphoma

Anti-idiotype × Anti-LFA-1 Bispecific Antibodies Inhibit Metastasis of B Cell Lymphoma

Anti-Idiotype × Anti-CD44 Bispecific Antibodies Inhibit Invasion of Lymphoid Organs by B Cell Lymphoma

Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis

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