Fibrillin-1, a novel TGF-beta-induced factor, is preferentially expressed in metaplastic carcinoma with spindle sarcomatous metaplasia

Lien, Huang-Chun; Lee, Yi‐Hsuan; Juang, Yu-Lin; Lu, Yueh-Tong

doi:10.1016/j.pathol.2019.02.001

Cited by 13 publications

(13 citation statements)

References 34 publications

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“…FBN1 and CD97 glycoprotein levels increased in AG‐PCa comparing to NAG‐PCa. These observations might be significant since CD97 were also overexpressed in post‐DRE urine of aggressive PCa [23], while FBN1 is elevated in other cancer types and the tumor promoting mechanism have been reported [37–41]. Our study represents the first report of elevated FBN1 in AG‐PCa urine.…”

Section: Discussionsupporting

confidence: 60%

Differentially expressed glycoproteins in pre‐ and post‐digital rectal examination urine samples for detecting aggressive prostate cancer

et al. 2023

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Urinary glycoproteins associated with aggressive prostate cancer (AG‐PCa) were previously reported using post‐digital rectal examination (DRE) urine specimens. To explore the potential of using pre‐DRE urine specimens for detecting AG‐PCa, we compared glycoproteins between pre‐ and post‐DRE urine specimens, verified the previously identified post‐DRE AG‐PCa‐associated urinary glycoproteins in pre‐DRE urine specimens, and explored potential new glycoproteins for AG‐PCa detection in pre‐DRE urine specimens. Quantitative glycoproteomic data were acquired for 154 pre‐DRE urine specimens from 41 patients with no cancer at biopsy, 48 patients with non‐AG‐PCa (Gleason score = 6), and 65 patients with AG‐PCa (Gleason score 7 or above). Compared to glycopeptides from the post‐DRE urine data, humoral immunity‐related proteins were enriched in pre‐DRE urine samples, whereas cell mediated immune response proteins were enriched in post‐DRE urine samples. Analyses of AG‐PCa‐associated glycoproteins from pre‐DRE urine revealed that the three urinary glycoproteins, prostate‐specific antigen (PSA), prostatic acid phosphatase (ACPP), and CD97 antigen (CD97) that were previously identified in post‐DRE urine samples, were also observed as AG‐PCa associated glycoproteins in pre‐DRE urine. In addition, we identified three new glycoproteins, fibrillin 1 (FBN1), vitronectin (VTN), and hemicentin 2 (HMCN2), to be potentially associated with AG‐PCa in pre‐DRE urine specimens. In summary, glycoprotein profiles differ between pre‐ and post‐DRE urine specimens. The identified AG‐PCa‐associated glycoproteins may be further evaluated in large cohort of pre‐DRE urine specimens for detecting clinically significant PCa.

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Section: Discussionsupporting

confidence: 60%

Differentially expressed glycoproteins in pre‐ and post‐digital rectal examination urine samples for detecting aggressive prostate cancer

et al. 2023

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“…FBN1, produced by fibroblasts, is an important structural factor of the extracellular matrix, which provides great support to connective tissues [43, 44]. As reported earlier, FBN1 mediated stretching of ligaments, skin, and blood vessels; supported rigid tissues, including muscle, nerve, and lens of the eyes; and regulated TGF‐β bioavailability [45], which induced epithelial‐to‐mesenchymal transition (EMT) in cancers of epithelial origin, thereby stimulating molecular and phenotypical changes that resulted in prometastatic characteristics [46, 47]. Moreover, the activation of TGF‐β is reported to enhance invasion of ovarian cancer [48].…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating studies have shown that FBN1 was highly expressed in some tumor types, such as mammary gland cancer [ 46 ] and papillary thyroid carcinoma [ 49 ], and participated in tumor progression [ 49 ]. Moreover, FBN1 promoted both ovarian tumorigenesis and metastasis in vivo and may serve as a biomarker for predicting recurrence of platinum‐sensitive ovarian cancer [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The Fibrillin‐1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells

Wang

Chen

Zuo

et al. 2022

Cancer Communications

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Background Chemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets. Methods RNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. Results FBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis. Conclusions The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

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“…The expression of phosphorylated Smad2/3 (pSmad2/3) is regarded as a marker of the occurrence of intracellular signal transduction via TGF-β, and Snail is one of the major transcription factors involved in the regulation of TGF-β-mediated EMT [13]. Fibronectin can serve as an indicator of the occurrence of EMT, where details on the expression of these molecules in SCP remain unknown [14,15].…”

Section: Introductionmentioning

confidence: 99%

Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report

et al. 2020

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Background Sarcomatoid carcinoma of the pancreas (SCP) tends to have similar or even worse prognosis than that of conventional pancreatic ductal adenocarcinoma. The clinical and pathological features of SCP remain poorly characterized owing to its rarity. Case presentation A 58-year-old man was admitted to our hospital with the chief complaints of upper abdominal pain and weight loss. Abdominal contrast computed tomography revealed a 5-cm low-density mass in the pancreatic body. Magnetic resonance cholangiopancreatography revealed an obstruction of the main pancreatic duct and a dilation of the distal main pancreatic duct. Based on the clinicoradiological findings, pancreatic body cancer was suspected, and the distal pancreatectomy was performed. A pathological examination revealed that the tumor was composed of an area of invasive ductal adenocarcinoma and an area of sarcomatous spindle-shaped cells; the latter component predominated. The spindle cells were immunohistochemically positive for both cytokeratin and vimentin, and thus, a pathological diagnosis of SCP was made. In addition, immunohistochemical analysis suggested the sarcomatous component might be derived from the adenocarcinoma component via the process of epithelial-mesenchymal transition. After the operation, the patient received 6 months of chemotherapy with gemcitabine. At 10 years after the operation, the patient is alive with no recurrence. Conclusions The current case study presented a SCP patient with long-term survival after the operation. It was worth noting that the sarcomatous component of the tumor pathologically showed lower MIB-1 labeling index compared with those in previously reported SCP cases, which might account for the long-term survival of the patient.

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Fibrillin-1, a novel TGF-beta-induced factor, is preferentially expressed in metaplastic carcinoma with spindle sarcomatous metaplasia

Cited by 13 publications

References 34 publications

Differentially expressed glycoproteins in pre‐ and post‐digital rectal examination urine samples for detecting aggressive prostate cancer

Differentially expressed glycoproteins in pre‐ and post‐digital rectal examination urine samples for detecting aggressive prostate cancer

The Fibrillin‐1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells

Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report

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