Comparison between the Gastric Cancer Cell Line MKN-45 and the High-Potential Peritoneal Dissemination Gastric Cancer Cell Line MKN-45P

Koga, Atsuhiko; Aoyagi, Keishiro; Imaizumi, T; Miyagi, Motoshi; Shirouzu, Kazuo

doi:10.2739/kurumemedj.58.73

Cited by 17 publications

(18 citation statements)

References 26 publications

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“…MKN-45P human gastric cancer cells were isolated from parental MKN-45P cells [32]. SKOV-3 human ovarian carcinoma and CT-26 mouse colon carcinoma cell lines were purchased from ATCC (SKOV-3 ATCC HBT-7; CT-26 ATCC CLR-2638).…”

Section: Methodsmentioning

confidence: 99%

Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles

Hunt

Simón‐Gracia

Tobi

et al. 2017

Journal of Controlled Release

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Gastrointestinal and gynecological malignancies disseminate in the peritoneal cavity - a condition known as peritoneal carcinomatosis (PC). Intraperitoneal (IP) administration can be used to improve therapeutic index of anticancer drugs used for PC treatment. Activity of IP anticancer drugs can be further potentiated by encapsulation in nanocarriers and/or affinity targeting with tumor-specific affinity ligands, such as tumor homing peptides. Here we evaluated a novel tumor penetrating peptide, linTT1 (AKRGARSTA), as a PC targeting ligand for nanoparticles. We first demonstrated that the primary homing receptor for linTTl, p32 (or gClqR), is expressed on the cell surface of peritoneal carcinoma cell lines of gastric (MKN-45P), ovarian (SKOV-3), and colon (CT-26) origin, and that peritoneal tumors in mice and clinical peritoneal carcinoma explants express p32 protein accessible from the IP space. Iron oxide nanoworms (NWs) functionalized with the linTT1 peptide were taken up and routed to mitochondria in cultured PC cells. NWs functionalized with linTT1 peptide in tandem with a pro-apoptotic [D(KLAKLAK)2] peptide showed p32-dependent cytotoxicity in MKN-45P, SKOV-3, and CT- 26 cells. Upon IP administration in mice bearing MKN-45P, SKOV-3, and CT-26 tumors, linTT1-functionalized NWs showed robust homing and penetration into malignant lesions, whereas only a background accumulation was seen in control tissues. In tumors, the linTT1-NW accumulation was seen predominantly in CD31-positive blood vessels, in LYVE-1-positive lymphatic structures, and in CD11b-positive tumor macrophages. Experimental therapy of mice bearing peritoneal MKN-45P xenografts and CT-26 syngeneic tumors with IP linTT1-D(KLAKLAK)2-NWs resulted in significant reduction of weight of peritoneal tumors and significant decrease in the number of metastatic tumor nodules, whereas treatment with untargeted D(KLAKLAK)2-NWs had no effect. Our data show that targeting of p32 with linTTl tumor-penetrating peptide improves tumor selectivity and antitumor efficacy of IP pro-apoptotic NWs. P32-directed intraperitoneal targeting of other anticancer agents and nanoparticles using peptides and other affinity ligands may represent a general strategy to increase their therapeutic index.

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Section: Methodsmentioning

confidence: 99%

Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles

Hunt

Simón‐Gracia

Tobi

et al. 2017

Journal of Controlled Release

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show abstract

“…MKN45P human gastric cancer cells were isolated from parental MKN45 cells and authenticated as described (30). MKN45P-luc cells were made by infecting MKN-45P cells with lenti-luciferase (Biogenova, Potomac, MD).…”

Section: Methodsmentioning

confidence: 99%

“…The protected maleimide initiator (Mal-Br) was prepared according to a previously published procedure (32). The Rhodamine 6G-based initiator (Rho-Br) was prepared according to a previously published procedure (30). ATRP synthesis and purification of P(OEG 10 MA) 20 -PDPA 90 from ME-Br, Rho-Br and Mal-Br initiators was carried out as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

Simón‐Gracia

Hunt

Scodeller

et al. 2016

Molecular Cancer Therapeutics

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Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer mortality, with a median survival of 1–3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here we employed flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with Paclitaxel® and in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to four months. In cell viability assay on cultured cancer cell lines (MKN-45P, SKOV3, CT26), Paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound Paclitaxel (Abraxane®). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of polymersomes-paclitaxel in treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with polymersome-Paclitaxel improved the therapeutic index of drug over Paclitaxel-Cremophor and Abraxane®, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions.

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“…MKN45P human gastric cancer cells with high peritoneal dissemination potential was isolated from parental MKN45 cells and authenticated as described (29, 30). MKN45P-luc cells were made by infecting MKN45P cells with lenti-luciferase (Biogenova, Potomac, MD).…”

Section: Methodsmentioning

confidence: 99%

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

Sugahara

Scodeller

Braun

et al. 2015

Journal of Controlled Release

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Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis.

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Comparison between the Gastric Cancer Cell Line MKN-45 and the High-Potential Peritoneal Dissemination Gastric Cancer Cell Line MKN-45P

Cited by 17 publications

References 26 publications

Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles

Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

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