L‐type amino acid transporter‐1 and <scp>CD</scp>98 expression in bone and soft tissue tumors

Koshi, Hiromi; Sano, Takaaki; Handa, Tadashi; Yanagawa, Takashi; Saitou, Kenichi; Nagamori, Shushi; Kanai, Yoshikatsu; Takagishi, Kenji; Oyama, Tetsunari

doi:10.1111/pin.12323

Cited by 21 publications

(17 citation statements)

References 22 publications

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“…The first barrier in cancer tissue involves the vascular blood wall, and extravasation from the bloodstream into the tumor tissue. After this EPR-driven leakage from blood vessels, the tumor environment (stromal tissue), i.e., acidic pH, facilitates liberation of free drugs that undergo rapid diffusion and reach tumor cells, after which transporter-driven rapid internalization occurs [1,3,30,31,54,57,59,72,73].…”

Section: Barriers To Delivery Of Drugs To Target Molecules In Tumor Cmentioning

confidence: 99%

A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects

2016

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Solid tumor has unique vascular architecture, excessive production of vascular mediators, and extravasation of macromolecules from blood vessels into the tumor tissue interstitium. These features comprise the phenomenon named the EPR effect of solid tumors, described in 1986. Our investigations on the EPR revealed that many mediators, such as bradykinin, NO, and prostaglandins, are involved in the EPR effect, which is now believed to be the most important element for cancer-selective drug delivery. However, tumors in vivo manifest great diversity, and some demonstrate a poor EPR effect, for example, because of impaired vascular flow involving thrombosis, with poor drug delivery and therapeutic failure. Another important element of this effect is that it operates in metastatic cancers. Because few drugs are currently effective against metastases, the EPR effect offers a great advantage in nanomedicine therapy. The EPR effect can also be augmented two to three times via nitroglycerin, ACE inhibitors, and angiotensin II-induced hypertension. The delivery of nanomedicines to tumors can thereby be enhanced. In traditional PDT, most PSs had low MW and little tumor-selective accumulation. Our hydroxypropylmetacrylamide-polymer-conjugated-PS, zinc protoporphyrin (apparent MW >50 kDa) showed tumor-selective accumulation, as revealed by fluorescent imaging of autochthonous cancers. After one i.v. injection of polymeric PS followed by two or three xenon light irradiation/treatments, most tumors regressed. Thus, nanoprobes with the EPR effect seem to have remarkable effects. Enhancing the EPR effect by using vascular modulators will aid innovations in PDT for greater tumor-targeted drug delivery.

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Section: Barriers To Delivery Of Drugs To Target Molecules In Tumor Cmentioning

confidence: 99%

A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects

2016

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“…In the canine lines, CD98 was not detected in the non-metastatic line but it was detected in the metastatic line indicating an increase. In OS, increased expression of CD98 has been observed in patient samples [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin

et al. 2017

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Osteosarcoma is the most common bone cancer in dogs and people. In order to improve clinical outcomes, it is necessary to identify proteins that are differentially expressed by metastatic cells. Membrane bound proteins are responsible for multiple pro-metastatic functions. Therefore characterizing the differential expression of membranous proteins between metastatic and non-metastatic clonal variants will allow the discovery of druggable targets and consequently improve treatment methodology. The objective of this investigation was to systemically identify the membrane-associated proteomics of metastatic and non-metastatic variants of human and canine origin. Two clonal variants of divergent in vivo metastatic potential from human and canine origins were used. The plasma membranes were isolated and peptide fingerprinting was used to identify differentially expressed proteins. Selected proteins were further validated using western blotting, flow cytometry, confocal microscopy and immunohistochemistry. Over 500 proteins were identified for each cell line with nearly 40% of the proteins differentially regulated. Conserved between both species, metastatic variants demonstrated significant differences in expression of membrane proteins that are responsible for pro-metastatic functions. Additionally, CD147, CD44 and vimentin were validated using various biochemical techniques. Taken together, through a comparative proteomic approach we have identified several differentially expressed cell membrane proteins that will help in the development of future therapeutics.

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“…There has been only one study investigating the expression of LAT1 and CD98 in sarcomas [13]. It reported that CD98 expression was higher than that of LAT1 in some bone tumors (67% vs. 47%, p<0.006); however, the percentage of CD98 expression was lower in soft tissue tumors than in bone tumors (28% vs. 67%).…”

Section: Discussionmentioning

confidence: 99%

“…The clinicopathological significance of LAT1 and CD98 expression in human epithelial tumors has been highlighted, but little is known about their expression in soft tissue tumors. Recently, Koshi et al immunohistochemically examined LAT1 and CD98 expression in 226 surgically-resected tumor tissues of bone and soft tissue origin [13], and reported that LAT1 and CD98 were positively expressed in 35% and 42% of these, respectively. They investigated the clinicopathological significance of these markers, using 4 samples of angiosarcoma; however, they did not draw any clear results regarding the expression of LAT1 and CD98.…”

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confidence: 99%

Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma

Shimizu¹,

Kaira²,

Okubo³

et al. 2017

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L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.

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L‐type amino acid transporter‐1 and CD98 expression in bone and soft tissue tumors

Cited by 21 publications

References 22 publications

A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects

A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next‐Generation Chemotherapeutics and Photodynamic Therapy—Problems, Solutions, and Prospects

Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin

Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma

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