Decreased Expression of the Low-density Lipoprotein Receptor-related Protein-1 (LRP-1) in Rats with Prostate Cancer

Gilardoni, Mónica Beatriz; Ceschin, Danilo Guillermo; Sahores, María M.; Oviedo, Mabel; Gehrau, Ricardo C.; Chiabrando, Gustavo A.

doi:10.1177/002215540305101201

Cited by 12 publications

(12 citation statements)

References 27 publications

(40 reference statements)

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“…Our study showed decreased expression of LRP1 in cell lines derived from non-small lung, prostate and colon carcinoma, all consistent with results described in literature [13,52,53]. The here first described ubiquitous expression of smLRP1 in tumour cell lines of different origins as well as human tissues (Fig 3A and 3B) extents our knowledge about LRP1.…”

Section: Discussionsupporting

confidence: 93%

“…Comparing tumour cells and corresponding healthy tissues showed differences in expression of smLRP1 and LRP1 (Fig 4A and 4B). LRP1 expression was decreased in cell lines derived from non-small lung, prostate, and colon carcinoma as described in literature [13,52,53]. Variations in LRP1 expression might be due to varying cell density at time of harvesting the cells [54].…”

Section: Discussionmentioning

confidence: 91%

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Verification and characterization of an alternative low density lipoprotein receptor-related protein 1 splice variant

Kolb¹,

Kurz²,

Schäfer³

et al. 2017

PLoS ONE

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BackgroundLow density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a ubiquitously expressed multi-ligand endocytosis receptor implicated in a wide range of signalling, among others in tumour biology. Tumour-associated genomic mutations of the LRP1 gene are described, but nothing is known about cancer-associated expression of LRP1 splice variants Therefore, the focus of this study was on an annotated truncated LRP1 splice variant (BC072015.1; NCBI GenBank), referred to as smLRP1, which was initially identified in prostate and lung carcinoma.MethodsUsing PCR and quantitative PCR, the expression of LRP1 and smLRP1 in different human tissues and tumour cell lines was screened and compared on tumour biopsies of head and neck squamous cell carcinoma (HNSCC). Using a recently developed anti-smLRP1 antibody, the expression of the putative LRP1 protein isoform in tumour cell lines in Western blot and immunofluorescence staining was further investigated.ResultsThe alternative transcript smLRP1 is ubiquitously expressed in 12 human cell lines of different origin and 22 tissues which is similar to LRP1. A shift in expression of smLRP1 relative to LRP1 towards smLRP1 was observed in most tumour cell lines compared to healthy tissue. The expression of LRP1 as well as smLRP1 is decreased in HNSCC cell lines in comparison to healthy mucosa. In vitro results were checked using primary HNSCC. Furthermore, the expression of the protein isoform smLRP1 (32 kDa) was confirmed in human tumour cell lines.ConclusionsSimilar to LRP1, the truncated splice variant smLRP1 is ubiquitously expressed in healthy human tissues, but altered in tumours pointing to a potential role of smLRP1 in cancer. Comparative results suggest a shift in expression in favour of smLRP1 in tumour cells that warrant further evaluation. The protein isoform is suggested to be secreted.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Verification and characterization of an alternative low density lipoprotein receptor-related protein 1 splice variant

Kolb¹,

Kurz²,

Schäfer³

et al. 2017

PLoS ONE

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“…For proliferation index and apoptosis index, the percentages of proliferating tenoblasts and apoptotic tenoblasts in all tenoblasts were calculated and the same was done for tenocytes. For the evaluation of protein expression in tenocytes and tenoblasts, an adapted scoring scheme was used (no detectable expression ϭ 0; detectable expression with the percentage of positive cells less than 10% ϭ 1; significant expression with the percentage of positive cells much higher than 10% ϭ 2) (Gilardoni et al 2003), and the results were presented as median scores. Because a paired comparison was employed, detectable expression in score 1 and significant expression in score 2 also referred to a direct comparison in staining intensity, i.e., if an obvious difference in staining intensity between elongated tendon cells and ovoid tendon cells was consistently noted, the higher staining intensity was scored 2 and the lower staining intensity was scored 1, even when the percentages of positive cells were similar.…”

Section: Image Analysismentioning

confidence: 99%

Immunohistochemical Characterization of Cells in Adult Human Patellar Tendons

Cheuk

Ping

et al. 2004

J Histochem Cytochem.

138

111

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S U M M A R Y Cells in tendons are conventionally identified as elongated tenocytes and ovoid tenoblasts, but specific markers for these cells are not available. The roles and interplay of these cells in tendon growth, remodeling, and healing are not well established. Therefore, we proposed to characterize these cells with respect to cell turnover, extracellular matrix metabolism, and expression of growth factors. Here we examined 14 healthy human patellar tendon samples for the expression of various proteins in tenocytes and tenoblasts, which were identified as elongated tendon cells and ovoid tendon cells, respectively. Matrix metalloproteinase 1 (MMP1), procollagen type I (procol I), heat shock protein 47 (hsp47), bone morphogenetic protein 12 (BMP12), 13 (BMP13), and transforming growth factor ␤ 1 (TGF ␤ 1) were detected by immunohistochemistry (IHC). An image analysis of the IHC staining for proliferation cell nuclear antigen (PCNA) and apoptotic cells was performed to determine the proliferation index and the apoptosis index in elongated and ovoid tendon cells. The ovoid tendon cells expressed higher levels of procol I, hsp47, MMP1, BMP12, BMP13, and TGF ␤ 1 than the elongated tendon cells. Both the proliferation index and the apoptosis index of ovoid tendon cells were higher than those of the elongated tendon cells. The results suggested that ovoid tendon cells, conventionally recognized as tenoblasts, were more active in matrix remodeling. The expression of BMP 12, BMP13 and TGF ␤ 1 might be associated with the different cellular activities of tenoblasts and tenocytes.

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“…Lipoprotein receptor related-protein 1 has already been attributed a role in cancer shortly after its discovery in 1988 ( Herz et al, 1988 ). Initially, several groups reported decreased LRP1 expression (Figure 1C ) levels in various cancer cell lines and tissues, thus assigning a tumor suppressive role to this receptor ( Kancha et al, 1994 ; de Vries et al, 1996 ; Gilardoni et al, 2003 ). These findings provided a rationale for earlier studies in which decreased binding and uptake of α 2 -macroglobulin (α 2 M), an LRP1 ligand, were observed in multiple cancer cell lines ( Van Leuven et al, 1979 ; Saksela et al, 1981 , 1984 ; Jensen et al, 1989 ).…”

Section: Lrp1 and Cancer: A Long But Difficult Marriagementioning

confidence: 99%

The Matricellular Receptor LRP1 Forms an Interface for Signaling and Endocytosis in Modulation of the Extracellular Tumor Environment

et al. 2015

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The membrane protein low-density lipoprotein receptor related-protein 1 (LRP1) has been attributed a role in cancer. However, its presumably often indirect involvement is far from understood. LRP1 has both endocytic and signaling activities. As a matricellular receptor it is involved in regulation, mostly by clearing, of various extracellular matrix degrading enzymes including matrix metalloproteinases, serine proteases, protease inhibitor complexes, and the endoglycosidase heparanase. Furthermore, by binding extracellular ligands including growth factors and subsequent intracellular interaction with scaffolding and adaptor proteins it is involved in regulation of various signaling cascades. LRP1 expression levels are often downregulated in cancer and some studies consider low LRP1 levels a poor prognostic factor. On the contrary, upregulation in brain cancers has been noted and clinical trials explore the use of LRP1 as cargo receptor to deliver cytotoxic agents. This mini-review focuses on LRP1’s role in tumor growth and metastasis especially by modulation of the extracellular tumor environment. In relation to this role its diagnostic, prognostic and therapeutic potential will be discussed.

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Decreased Expression of the Low-density Lipoprotein Receptor-related Protein-1 (LRP-1) in Rats with Prostate Cancer

Cited by 12 publications

References 27 publications

Verification and characterization of an alternative low density lipoprotein receptor-related protein 1 splice variant

Verification and characterization of an alternative low density lipoprotein receptor-related protein 1 splice variant

Immunohistochemical Characterization of Cells in Adult Human Patellar Tendons

The Matricellular Receptor LRP1 Forms an Interface for Signaling and Endocytosis in Modulation of the Extracellular Tumor Environment

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