Organ-Specific Requirements for Cell Adhesion Molecules During Lymphoma Cell Dissemination

Naor, David; Sionov, Ronit Vogt; Zahalka, Muayad A.; Rochman, Mark; Holzmann, Bernhard; Ish-Shalom, Dvorah

doi:10.1007/978-3-642-71987-5_9

Cited by 10 publications

(9 citation statements)

References 68 publications

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“…The reaction was stopped by the addition of Tris base. The digestion mixture was analyzed by SDS-PAGE to verify complete digestion and purity of F(abЈ) 2 . The hybridoma cell line M17/4.4 (M17), secreting a rat mAb against the ␣ subunit of murine LFA-1, was obtained from American Type Culture Collection (Manassas, VA).…”

Section: Cell Lines and Absmentioning

confidence: 99%

“…Since normal lymphocytes circulate continuously and extravasate into lymphoid organs and inflamed tissues, it is conceivable that mechanisms of normal lymphocyte homing operate in dissemination of their malignant counterparts. Increasing evidence indicates that adhesion molecules, involved in normal lymphocyte trafficking, have an essential role in lymphoma dissemination (1)(2)(3). Moreover, adhesion molecules are involved in postextravasation events that control progression and growth after homing to the target organ (4).…”

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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: Cell Lines and Absmentioning

confidence: 99%

mentioning

confidence: 99%

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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“…Cellular effects of HA on tumor cells are largely mediated by HA receptors or hyaladherins , the most characterized of which are CD44 and Rhamm. Both of these receptors, which regulate signaling through Ras and other small GTPases (Gares and Pilarski, 2000;Turley et al, 2002;Ponta et al, 2003), are linked to fibroproliferative (Lovvorn et al, 1998) and neoplastic processes (Naor et al, 1998). Rhamm (Hardwick et al, 1992), the first cellular HAbinding protein identified, was originally referred to as HABP (hyaluronan-binding protein, Turley, 1982), then later designated as HMMR (for human Rhamm, Spicer et al, 1995), IHABP/Rhamm (Assmann et al, 1999) for intracellular Rhamm, and CD168 for the cell surface form of Rhamm.…”

Section: Introductionmentioning

confidence: 99%

Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor)

et al. 2003

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Aggressive fibromatosis (desmoid tumor) is a locally invasive soft tissue neoplasm associated with mutations resulting in b-catenin-mediated transcriptional activation. This tumor is composed of cells with histological and molecular characteristics common to proliferating mesenchymal cells of dermal wounds. Using immunohistochemistry and RT-PCR, we show that Rhamm, a protein with an important role in wound healing and neoplastic progression, is also expressed at high levels in aggressive fibromatosis. A mouse harboring a targeted deletion in Rhamm was generated, resulting in viable RhammÀ/À animals. RhammÀ/À mice were crossed with Apc/ Apc1638N mice, which harbor a targeted mutation in the Apc gene predisposing animals to gastrointestinal and aggressive fibromatosis tumors. Rhamm deficiency significantly decreased the number of aggressive fibromatosis tumors formed, but did not alter the number of gastrointestinal polyps. Cell culture studies show that Rhamm regulates cell proliferation in both fibroblasts and fibromatosis cells under conditions of low density, but not high density. These results suggest that Rhamm regulates proliferation of cells with sparse cell-cell contacts, such as occurs in aggressive fibromatosis; provides the first genetic evidence implicating Rhamm in tumor pathology; and suggest Rhamm blockade as a potential therapeutic target for this otherwise difficult-totreat neoplasm.

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“…Because normal lymphocytes circulate continuously and extravasate into lymphoid organs and into inflamed tissues, it is conceivable that mechanisms of normal lymphocyte homing operate in dissemination of their malignant counterparts. Increasing evidence indicates that adhesion molecules, involved in normal lymphocyte trafficking, have an essential role in lymphoma dissemination (1)(2)(3). Moreover, adhesion molecules are involved in postextravasation events that control progression and growth after homing to the target organ (4).…”

mentioning

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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Organ-Specific Requirements for Cell Adhesion Molecules During Lymphoma Cell Dissemination

Cited by 10 publications

References 68 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

Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor)

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

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