Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression

Cuadros, Thaïs; Trilla, E.; Vilà, Maria Rosa; Torres, Inés de; Vilardell, J; Messaoud, Nabil Ben; Salcedo, Mayte; Sarró, Eduard; López-Hellı́n, Joan; Blanco, Albert; Mir, Carmen; Cajal, Santiago Ramón y; Itarte, Emilio; Moróte, Juan; Meseguer, Anna

doi:10.1016/j.ejca.2012.12.020

Cited by 24 publications

(20 citation statements)

References 25 publications

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“…Importantly, we did not find any evidence suggesting that soluble KIM-1 can serve as a PtdSer opsonin like MFG-E8 and Gas6 to promote efferocytosis by PTECs that do not express KIM-1 (78). However, our data do not exclude the possibility that shed KIM-1 might have a nonphagocytic role during AKI or in cancers of the kidney (15). Nevertheless, the fact that pretreatment with TAPI-0 rescued the inhibitory effect of H 2 O 2 and PV on KIM-1-mediated efferocytosis suggests that the reduction in phagocytosis is independent of other potential effects of these agents on cells and is dependent on KIM-1 shedding.…”

Section: Discussioncontrasting

confidence: 85%

“…Next, we proceeded to characterize the sheddase responsible for KIM-1 proteolysis in RCC cells expressing endogenous KIM-1 (15,84). Based on the inhibitory effect of hyroxamate-based metalloprotease inhibitors on KIM-1 shedding (7,36,39) and the knowledge that ADAM17 or TACE mediates PMA-induced shedding of various transmembrane proteins (22,80,85), we hypothesized that TACE/ ADAM17 may be responsible for regulating KIM-1 shedding.…”

Section: -P Cellsmentioning

confidence: 99%

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Accelerated receptor shedding inhibits kidney injury molecule-1 (KIM-1)-mediated efferocytosis

Gandhi

et al. 2014

American Journal of Physiology-Renal Physiology

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Efficient clearance of apoptotic cells (efferocytosis) prevents inflammation and permits repair following tissue injury. Kidney injury molecule-1 (KIM-1) is a receptor for phosphatidylserine, an “eat-me” signal exposed on the surface of apoptotic cells that marks them for phagocytic clearance. KIM-1 is upregulated on proximal tubule epithelial cells (PTECs) during ischemic acute kidney injury (AKI), enabling efferocytosis by surviving PTECs. KIM-1 is spontaneously cleaved at its ectodomain region to generate a soluble fragment that serves a sensitive and specific biomarker for AKI, but the biological relevance of KIM-1 shedding is unknown. Here, we sought to determine how KIM-1 shedding might regulate efferocytosis. Using cells that endogenously and exogenously express KIM-1, we found that hydrogen peroxide-mediated oxidative injury or PMA treatment accelerated KIM-1 shedding in a dose-dependent manner. KIM-1 shedding was also accelerated when apoptotic cells were added. Accelerated shedding or the presence of excess soluble KIM-1 in the extracellular milieu significantly inhibited efferocytosis. We also identified that TNF-α-converting enzyme (TACE or ADAM17) mediates both the spontaneous and PMA-accelerated shedding of KIM-1. While accelerated shedding inhibited efferocytosis, we found that spontaneous KIM-1 cleavage does not affect the phagocytic efficiency of PTECs. Our results suggest that KIM-1 shedding is accelerated by worsening cellular injury, and excess soluble KIM-1 competitively inhibits efferocytosis. These findings may be important in AKI when there is severe cellular injury.

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Section: Discussioncontrasting

confidence: 85%

Section: -P Cellsmentioning

confidence: 99%

Accelerated receptor shedding inhibits kidney injury molecule-1 (KIM-1)-mediated efferocytosis

Gandhi

et al. 2014

American Journal of Physiology-Renal Physiology

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“…In this study, we explored the potential of TIM-1 as an ADC target and described the development and characterization of CDX-014, an ADC composed of a human IgG1k mAb specific for TIM-1, covalently linked to the enzyme-cleavable microtubule inhibitor vcMMAE. Several studies have documented that TIM-1 expression is selectively upregulated on the plasma membrane of renal cell and clear cell ovarian carcinomas and has been associated with poor prognosis, making TIM-1 a tractable target for an antibody-based approach (15,(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

“…TIM-1 expression is upregulated in several human cancers, most notably in renal cell carcinoma (RCC), including metastatic RCC, and ovarian clear cell carcinoma (15,18). Furthermore, TIM-1 expression is associated with a more malignant phenotype of RCC, and shedding of the ectodomain has been associated with tumor progression (19,20). Overexpression of TIM-1 in clear cell RCC (ccRCC) lines activated the IL6/STAT-3/HIF-1A pathway apparently dependent on TIM-1 shedding, and phosphorylation of serine 727 of STAT-3 in ccRCC patients was correlated with clinical outcome (21).…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Antibody–Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1

Thomas

Vitale

O’Neill

et al. 2016

Molecular Cancer Therapeutics

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T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody-drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1-expressing cell lines, but not on TIM-1-negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1-expressing tumors. Mol Cancer Ther; 15(12); 2946-54. ©2016 AACR.

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“…However, only rats aestheticized by isoflurane showed an increase in HAVCR-1, also known as kidney injury molecule 1 after 72 hr. Both molecules are studied as biomarkers for kidney injury (Han, Bailly, Abichandani, Thadhani, & Bonventre, 2002), carcinoma (Cuadros et al, 2013), and urinary tract dysfunction (Steigedal et al, 2014).…”

Section: Halogenated Anesthesiamentioning

confidence: 99%

Renal effects of general anesthesia from old to recent studies

Alizadeh

Fard

2019

Journal Cellular Physiology

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Various types of anesthesia are being utilized to maintain physiologically secured surgical conditions. Nearly all categories of general anesthesia are characterized by various perioperative and postoperative complications. These shortcomings are important aspects that need to be considered by the anesthesiologist and surgeon before administration of these compounds. The renal effects of anesthesia play an important role in understanding possible systemic changes due to the fact that the kidney has a direct or indirect impact on nearly all the systems of the body. Various studies have been conducted to find out changes in renal parameters and its systemic effects upon administration of the anesthesia and its postoperative repercussions. Besides that, the impaired renal function might have an impact on the excretion of anesthetic metabolites, which can lead to long‐term dysfunction. Patients with a previous history of disease ought to be brought under consideration because these chemicals can ameliorate pre‐existent symptoms. This review is intended to discuss the early and latest studies based on the effects of general anesthesia on the renal system.

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Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression

Cited by 24 publications

References 25 publications

Accelerated receptor shedding inhibits kidney injury molecule-1 (KIM-1)-mediated efferocytosis

Accelerated receptor shedding inhibits kidney injury molecule-1 (KIM-1)-mediated efferocytosis

Development of a Novel Antibody–Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1

Renal effects of general anesthesia from old to recent studies

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