Establishment of a new human cancer cell line secreting protease nexin‐II/amyloid β protein precursor derived from squamous‐cell carcinoma of lung

Itoh, Hiroshi; Kataoka, Hiroaki; Koita, Hiroyuki; Nabeshima, Kazuki; Inoue, Teruhiko; Kangawa, Kenji; Koono, Masashi

doi:10.1002/ijc.2910490322

Cited by 27 publications

(19 citation statements)

References 35 publications

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“…In fact, we have previously purified HMTI from SFCM of the LC-l/sq cell line and confirmed it to be PN-II/APP by N-terminal amino-acid sequencing (Itoh et al, 1991). It should be noted that the 43-kDa band and the 90-to 100-kDa weak band of T-24 and CoCM-I, respectively, were also recognized FIGURE 2 -Reverse zymography for trypsin inhibitors in SFCM of human carcinoma cell lines.…”

Section: Analysis Of Sfcm Of Human Tumor-cell Linesmentioning

confidence: 77%

Reverse‐zymographic analysis of protease nexin‐II/amyloid β protein precursor of human carcinoma cell lines, with special reference to the grade of differentiation and metastatic phenotype

Kataoka

Seguchi

Iwamura

et al. 1995

Intl Journal of Cancer

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Trypsin inhibitors in serum-free conditioned media (SFCM) of various human carcinoma cell lines were analyzed by reverse zymography. Most of the cells secreted high-molecular-weight trypsin inhibitors (HMTI) larger than 100 kDa. The cell lines of colorectal carcinoma origin had a tendency to secrete HMTI whose molecular weight was a little higher than that of the other cell lines. Analysis of SFCM of subclones with different histological differentiation and metastatic/invasive potentials derived from a single pancreatic carcinoma cell line SUIT-2 showed that the HMTI activity in SFCM was correlated to the degree of histological differentiation in vivo and tended to be inversely correlated to their metastatic/invasive capabilities. Immunoblotting analysis revealed that these HMTI were protease nexin-II/amyloid beta protein precursors (PN-II/APP). Semi-quantificative reverse-transcriptase/polymerase-chain reaction study for PN-II/APP mRNAs suggested that the differences in PN-II/APP activities in SFCM between the subclones might be post-transcriptional or post-secretional events. In addition, SFCM of a highly metastatic subclone contained 43-kDa protein which reacted to anti-APP monoclonal antibody (MAb) suggesting that the subclone may have APP-degrading activity.

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Section: Analysis Of Sfcm Of Human Tumor-cell Linesmentioning

confidence: 77%

Reverse‐zymographic analysis of protease nexin‐II/amyloid β protein precursor of human carcinoma cell lines, with special reference to the grade of differentiation and metastatic phenotype

Kataoka

Seguchi

Iwamura

et al. 1995

Intl Journal of Cancer

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“…APP also seems to function as a local mediator of growth in several malignant tumors such as lung (6), colon (20), parathyroid (21), pancreas (22), oral (23), and thyroid cancers (24). Nevertheless, the transcriptional regulation of APP has not been well investigated.…”

Section: Discussionmentioning

confidence: 99%

“…The studies using fibroblasts revealed that APP is secreted to the cell culture medium and have an autocrine function in growth regulation (4). The secreted APP is also observed in the culture medium of tumor cells such as rat pheochromocytoma PC12 cells (5) and human lung squamous cell carcinoma cells (6).…”

Section: Introductionmentioning

confidence: 99%

Amyloid Precursor Protein Is a Primary Androgen Target Gene That Promotes Prostate Cancer Growth

et al. 2008

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Androgen receptor (AR) is a critical transcription factor that regulates various target genes and contributes to the pathophysiology of prostate cancer hormone dependently. Here, we identify amyloid precursor protein (APP) as a primary androgen target through chromatin immunoprecipitation (ChIP) combined with genome tiling array analysis (ChIPchip). ChIP-treated DNA were obtained from prostate cancer LNCaP cells with R1881 or vehicle treatment using AR or acetylated histone H3 antibodies. Ligand-dependent AR binding was further enriched by PCR subtraction. Using chromosome 21/22 arrays, we identified APP as one of the androgen-regulated genes with adjacent functional AR binding sites. APP expression is androgen-inducible in LNCaP cells and APP immunoreactivity was correlated with poor prognosis in patients with prostate cancer. Gain-of-function and lossof-function studies revealed that APP promotes the tumor growth of prostate cancer. The present study reveals a novel APP-mediated pathway responsible for the androgendependent growth of prostate cancer. Our findings will indicate that APP could be a potential molecular target for the diagnosis and treatment of prostate cancer. [Cancer Res 2009;69(1):137-42]

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“…Soluble APPα has been found to be secreted in copious amount in various human cancer cell lines [51]. It has also been linked to promoting abnormal cell growth in pancreatic cancer cells via various MAP kinase or protein kinase C signaling pathways [44], as well as in a number of solid cancers [129].…”

Section: App Proteolytic Fragmentsmentioning

confidence: 99%

The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes

2014

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The amyloid precursor protein (APP) has occupied a central position in Alzheimer’s disease (AD) pathophysiology, in large part due to the seminal role of amyloid-β peptide (Aβ), a proteolytic fragment derived from APP. Although the contribution of Aβ to AD pathogenesis is accepted by many in the research community, recent studies have unveiled a more complicated picture of APP’s involvement in neurodegeneration in that other APP-derived fragments have been shown to exert pathological influences on neuronal function. However, not all APP-derived peptides are neurotoxic, and some even harbor neuroprotective effects. In this review, we will explore this complex picture by first discussing the pleiotropic effects of the major APP-derived peptides cleaved by multiple proteases, including soluble APP peptides (sAPPα, sAPPβ), various C- and N-terminal fragments, p3, and APP intracellular domain fragments. In addition, we will highlight two interesting sequences within APP that likely contribute to this duality in APP function. First, it has been found that caspase-mediated cleavage of APP in the cytosolic region may release a cytotoxic peptide, C31, which plays a role in synapse loss and neuronal death. Second, recent studies have implicated the –YENPTY– motif in the cytoplasmic region as a domain that modulates several APP activities through phosphorylation and dephosphorylation of the first tyrosine residue. Thus, this review summarizes the current understanding of various APP proteolytic products and the interplay among them to gain deeper insights into the possible mechanisms underlying neurodegeneration and AD pathophysiology.

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Establishment of a new human cancer cell line secreting protease nexin‐II/amyloid β protein precursor derived from squamous‐cell carcinoma of lung

Cited by 27 publications

References 35 publications

Reverse‐zymographic analysis of protease nexin‐II/amyloid β protein precursor of human carcinoma cell lines, with special reference to the grade of differentiation and metastatic phenotype

Reverse‐zymographic analysis of protease nexin‐II/amyloid β protein precursor of human carcinoma cell lines, with special reference to the grade of differentiation and metastatic phenotype

Amyloid Precursor Protein Is a Primary Androgen Target Gene That Promotes Prostate Cancer Growth

The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes

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