Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Reduces Adhesion and Invasion of Metastatic Lung, Cervix, Colon and Prostate Cancer Cells

Omar, Aadilah; Reusch, Uwe; Knackmuss, Stefan; Little, Melvyn; Weiß, Stefan

doi:10.1016/j.jmb.2012.02.035

Cited by 46 publications

(58 citation statements)

References 23 publications

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“…Alternatively, both antibodies suppressed A20 cell attachment to components of the extracellular matrix especially laminin. Inhibition of laminin attachment is consistent with what has been reported previously with antibodies that targets both the immature and mature forms of the laminin receptor protein [29][30][31] or with treatments that down-regulate expression of the 37 k D /67 kD laminin receptor. 30 If such inhibition occurred in the circulation, it might delay tumor cell egress from the blood stream and as a consequence, lead to more efficient intravascular cell killing (by whatever mechanisms).…”

Section: Discussionsupporting

confidence: 90%

Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

McClintock

Warner

Ali

et al. 2015

Cancer Biology & Therapy

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The oncofetal antigen -immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While the antibodies were modestly effective at preventing tumor growth at the primary injection site, both antibodies strongly suppressed end-organ tumor formation following intravenous tumor cell injection. Capacity of anti-OFA/iLRP antibodies to suppress tumor spread through the blood in the leukemia model suggests their use as a therapy for individuals with leukemic disease (either for patients in remission or even as part of an induction therapy). The results also suggest use against metastatic spread with solid tumors.

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Section: Discussionsupporting

confidence: 90%

Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

McClintock

Warner

Ali

et al. 2015

Cancer Biology & Therapy

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“…Cells adhere to the ECM via the action of ECM receptors[2]. Particularly, the non-integrin 37-kDa/67-kDa laminin receptor (LRP/LR) is a major component of the extracellular matrix, assisting in numerous physiological processes[3], [4], [5]. It is suggested that 37-kDa LRP is the precursor of the 67-kDa high affinity laminin receptor LR, however, the exact mechanism by which the precursor forms the receptor is unknown[6].…”

Section: Introductionmentioning

confidence: 99%

“…In the nucleus, LRP/LR plays a critical role in the maintenance of nuclear structures whilst in the cytosol, it assists in translational processes[8]. As a transmembrane receptor, LRP/LR serves several functions such as cell migration[9], cell-matrix adhesion[10], cell viability and proliferation[3], [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

et al. 2014

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Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction.

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“…This increased interaction subsequently leads to increased adhesion, followed by activation of Type IV collagenase, leading to degradation of the basement membrane and invasion by the tumorigenic cells (28). Overexpression of LRP/LR, when compared with noninvasive tumorigenic cells, has been observed in various invasive tumors, including pancreatic cancer cells (29); colon, lung, prostate and cervical cancer cells (30); esophageal and breast cancer cells (31); and liver cancer cells (8).…”

mentioning

confidence: 99%

“…Additionally, it has been found that IgG1-iS18, the full-length anti-LRP/LR-specific antibody, exhibits a significant effect on hampering the LRP/LR-laminin-1 interaction in various cancers, including early-stage colorectal cancer (30).…”

mentioning

confidence: 99%

Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Impedes Adhesion and Invasion in Early- and Late-Stage Colorectal Carcinoma Cells

Vania

Chetty

Ferreira

et al. 2016

Mol Med

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Cancer is a highly complex disease that has become one of the leading causes of death globally. Metastasis, a major cause of cancer deaths, requires two crucial events, adhesion and invasion. The 37kDa/67kDa laminin receptor (laminin receptor precursor/high-affinity laminin receptor [LRP/LR]) enhances these two steps, consequently aiding in cancer progression. In this study, the role of LRP/LR in adhesion and invasion of early-stage (SW-480 and HT-29) and late-stage (DLD-1) colorectal cancer cells was investigated. Western blotting revealed that early-and late-stage colorectal cancer cells contained significantly higher total LRP/LR levels compared with poorly invasive MCF-7 breast cancer control cells. Flow cytometry revealed that both stages of colorectal cancer displayed significantly higher cell surface LRP/LR levels. Furthermore, upon treatment of colorectal cancer cells with the anti-LRP/LR-specific antibody IgG1-iS18, adhesion to laminin-1 was significantly reduced in both stages. Each stage's invasive potential was determined using the Matrigel™ invasion assay, showing that invasion was significantly impeded in both colorectal cancer stages when the cells were incubated with IgG1-iS18. In addition, Pearson's correlation coefficients propose that both total and cell surface LRP/LR levels are directly proportional to the adhesive and invasive potential of both stages of colorectal cancer. Hence, these findings indicate potential for use of the IgG1-iS18 antibody as a promising therapeutic tool for colorectal cancer patients at both stages.

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Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Reduces Adhesion and Invasion of Metastatic Lung, Cervix, Colon and Prostate Cancer Cells

Cited by 46 publications

References 23 publications

Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Impedes Adhesion and Invasion in Early- and Late-Stage Colorectal Carcinoma Cells

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