Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells

Authors: Thalia M. Rebelo, Carryn J. Chetty, Eloise Ferreira, Stefan F. T. Weiss

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Cancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps. The current study investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive potential.

Methods

AsPC-1 and IMR-32 cells were utilized as the experimental cell lines for the study. Cell surface LRP/LR levels were visualised and quantified on the experimental and control (MCF-7) cell lines via confocal microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell lines were assessed by Western blotting and the adhesive and invasive potential of the above-mentioned cell lines was determined before and after supplementation with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the data was confirmed via the use of the two-tailed student’s t-test and Pearson’s correlation coefficient.

Results

Flow cytometry revealed that AsPC-1 and IMR-32 cells displayed significantly higher cell surface LRP/LR levels in comparison to the MCF-7 control cell line. However, Western blotting and subsequent densitometric analysis revealed that all three tumorigenic cell lines displayed no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR-32 cells with IgG1-iS18 caused a significant reduction in the adhesive and invasive potential of the cells to laminin-1 and through the ECM-like Matrigel™, respectively. Pearson’s correlation coefficients indicated a high correlation, thus suggesting a directly proportional relationship between cell surface LRP/LR levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.

Conclusion

These findings suggest that through the interference of the LRP/LR-laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an alternative therapeutic tool for the treatment of metastatic pancreatic cancer and neuroblastoma.
Literature
1.
Chao DL, Sanchez CA, Galipeau PC, Blount PL, Paulson TG, Cowan DS, et al. Cell proliferation, cell cycle abnormalities, and caner outcome in patients with Barrett’s oesophagus: a long-term prospective study. Clin Cancer Res. 2008;14:6988–95.CrossRefPubMedPubMedCentral
2.
3.
Jemal A, Bray F, Melissa M, Ferlay J, Ward E, Forman D. Global Cancer Statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
4.
5.
Gauczynski S, Peyrin J-M, Haïk S, Leucht C, Hundt C, Rieger R, Krasemann S, Deslys J-P, Dormont D, Lasmézas CI, Weiss S. The 237 kDa/67 kDa laminin receptor acts as the cell surface receptor for the cellular prionprotein. EMBO J. 2001;20:5863–75.CrossRefPubMedPubMedCentral
6.
Hundt C, Peyrin J-M, Haïk S, Gauczynski S, Leucht C, Rieger R, Riley M-L, Deslys J-P, Dormont D, Lasmézas CI, Weiss S. Identification of interaction domains of the prion protein with its 37 kDa/67 kDalaminin receptor. EMBO J. 2001;20:5876–86.CrossRefPubMedPubMedCentral
7.
Jovanovic K, Chetty CJ, Khumalo T, Da Costa DB, Ferreira E, Malindisa ST, et al. Novel patented therapeutic approaches targeting the 37 kDa/67 kDa laminin receptor for treatment of Cancer and Alzheimer’s Disease. Expt Opin Ther Patents. 2015;25(5):567–82.CrossRef
8.
Buto S, Tagliabue E, Ardini E, Magnifico A, Ghirelli C, et al. Formation of the 67- kDa laminin receptor by acylation of the precursor. J Cell Biochem. 1998;69:244–51.CrossRefPubMed
9.
Omar A, Reusch U, Knackmuss S, Little M, Weiss SFT. Anti-LRP.LR specific antibody IgG1-iS18 significantly reduces adhesion and invasion of metastatic lung, cervix, colon and prostate cancer cells. J Mol Biol. 2012;419:102–9.CrossRefPubMed
10.
Vania L, Chetty CJ, Ferreira E , Weiss SFT. Anti-LRP/LR specific antibody IgG1-iS18 significantly impedes adhesion and invasion in early and late stage colorectal carcinoma cells. Mol Med. 2016; 22: 664–73.
11.
Khumalo T, Reusch U, Knackmuss S, Little M, Veale RB, Weiss SFT. Adhesion and invasion of breast and oesophageal cancer cells are impeded by anti-LRP/LR-specific antibody IgG1-iS18. PLoS One. 2013;8(6):e66297.CrossRefPubMedPubMedCentral
12.
Chetty C, Khumalo T, Da Costa DB, Reusch U, Knackmuss S, Little M, Weiss SFT. Anti-LRP/LR specific antibody lgG1-iS18 impedes adhesion and invasion of liver cancer cells. PLoS One. 2014. doi:10.​1371/​journal.​pone.​0096268.
13.
Mbazima V, Da Costa DB, Omar A, Jovanovic K, Weiss SFT. Interactions between PrPc and other ligands with the 37-kDa/67-kDa laminin receptor. Front Biosci. 2010;15:1150–63.CrossRef
14.
Omar A, Jovanovic K, Da Costa DB, Gonsalves D, Moodley K, Caveney R. Patented biological approaches for the therapeutic modulation of the 37-kDA/67-kDa laminin receptor. Expert Opin Ther Pat. 2011;21:35–53.CrossRefPubMed
15.
Vana K, Zuber C, Planz H, Kolodziejczak D, Zemora G, Bergmann AK, Weiss SFT. LRP/LR as an alternative promising target in therapy of prion diseases, Alzheimer’s disease and cancer. Inf Disorder Drug Targets. 2009;9:69–80.CrossRef
16.
Da Costa DB, Jovanovic K, Gonsalves D, Moodley K, Reusch U, Knackmuss S, et al. Anti- LRP/LR specific antibody IgG1-iS18 and knock-down of LRP/LR by shRNAs rescue cells from Abeta42 induced cytotoxicity. Sci Rep. 2013;3:2702.
17.
Jovanovic K, Loos B, Da Costa DB, Penny C, Weiss SFT. High resolution imaging study of interactions between the 37 kDa/67kDa Laminin Receptor and APP, beta-secretase and gamma-secretase in Alzheimer’s disease. PLoS One. 2014;9(6):e100373.CrossRefPubMedPubMedCentral
18.
Naidoo K, Malindisa ST, Otgaar TC, Bernert M, Da Costa Dias B, Ferreira E, et al. Knock-down of the 37 kDa/67kDa laminin receptor LRP/LR impedes telomerase activity. PLoS ONE. 2015; in press.
19.
Givant-Horwitz V, Davidson B, Reich R. Laminin-Induced Signaling in Tumor cells: The Role of the Mr 67, 000 Laminin Receptor. Cancer Res. 2004;64:3572–9.CrossRefPubMed
20.
Liotta LA, Stetler SW. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 1991;51:50545–95.
21.
Ardini E, Sporchia B, Pollegioni L, Modugno M, Ghirelli C, Castiglioni F. Identification of a novel function for 67-kDaq laminin receptor: increase in laminin degradation rate and release of motility fragments. Cancer Res. 2002;62:1321–5.PubMed
22.
Ziober BL, Lin CS, Kramer RH. Laminin-binding integrins in tumor progression and metastasis. Semin Cancer Biol. 1996;7:119–28.CrossRefPubMed
23.
Zuber C, Mitteregger G, Schuhmann N, Rey C, Knackmuss S, Rupprecht W, Reusch U, Pace C, Little M, Kretzschmar HA, Hallek M, Büning H, Weiss S. Delivery of single-chain antibodies (scFvs) directed against the 37/67 kDa laminin receptor into mice via recombinant adeno-associated viral vectors for prion disease gene therapy. J Gen Virol. 2008;89(Pt 8):2055–61.CrossRefPubMed
24.
Stetler-Stevenson M, Mansoor A, Lim M, Fukushima P, Kehrl J, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells. Blood. 1997;89:1708–15.PubMed
Metadata
Title
Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells
Authors
Thalia M. Rebelo
Carryn J. Chetty
Eloise Ferreira
Stefan F. T. Weiss
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2953-2

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

The triptolide derivative MRx102 inhibits Wnt pathway activation and has potent anti-tumor effects in lung cancer

Debate

Primary extramammary invasive Paget’s vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

Research article

Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer

Research article

Patterns of recurrence after selective postoperative radiation therapy for patients with head and neck squamous cell carcinoma

Case report

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma

Research article

Type 2 diabetes mellitus and risk of colorectal adenoma: a meta-analysis of observational studies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits