Dataset Information

Probing of the expression of the low-density lipoprotein receptor in vivo using an anti-receptor monoclonal antibody.

ABSTRACT: MAC188 is a rat anti-[low-density lipoprotein (LDL) receptor] monoclonal antibody (McAb) which binds to the cell surface receptor with high affinity at physiological temperatures, even in the presence of high concentrations of the natural ligand, LDL. Binding of McAb MAC188 at 37 degrees C is followed by internalization and intracellular sequestering of the receptor, which results in the transient disappearance of the receptor from the cell surface. The high binding affinity and epitope specificity of McAb MAC188 suggested that this antibody could be used to quantify receptor expression in vivo. Mixtures of radiolabelled anti-receptor antibody and a control McAb (MAC221) were injected intravenously into rabbits, and the clearance from serum and uptake into tissues was determined. A fraction of the anti-receptor McAb was cleared rapidly from the circulation by a high-affinity and saturable (receptor-dependent) process. Receptor-dependent uptake of the anti-receptor McAb was measurable in liver, adrenal glands, kidneys, spleen, kidney, thoracic aorta and heart. It was highest in liver and adrenal glands and correlated well with the level of receptor protein and the rate of LDL transport in individual tissues. Anti-receptor McAbs such as MAC188, with suitable domain specificity and binding affinity at physiological temperatures, have important advantages over the natural ligand as tracers for the receptor in vivo, and may find widespread applications in studies of the receptor status (activity) in animals and man.

SUBMITTER: Gherardi E

PROVIDER: S-EPMC1130591 | biostudies-other | 1991 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Background Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken–mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. Methods We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. Results High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35–9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm3versus 726.3 mm3, p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2. Conclusions Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09789-6.

Dataset Information

Probing of the expression of the low-density lipoprotein receptor in vivo using an anti-receptor monoclonal antibody.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets