High Incidence of Lymph-node Metastasis in a Pancreatic-cancer Patient-derived Orthotopic Xenograft (PDOX) NOG-Mouse Model.

Abstract

BACKGROUND/AIM:

Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) model. An important goal of PDOX-model development is facile visualization of metastasis in live mice. In the present report we evaluated tumor growth and metastasis in pancreatic cancer PDOX NOG [Non-obese diabetes (NOD)/Scid/IL2Rγnull]-and nude-mouse models using red fluorescent protein (RFP)-expressing tumor stroma to visualize the primary tumor and metastasis.

MATERIALS AND METHODS:

A patient-derived pancreatic cancer was initially implanted in transgenic RFP-expressing nude mice. Then, tumor fragments, which acquired RFP expressing stroma while growing in RFP-expressing nude mice were orthotopically implanted in nude and NOG mice. The primary pancreatic tumor and metastasis were observed 8 weeks after implantation.

RESULTS:

Lymph-node metastases expressing red fluorescence were detected only in NOG mice. Significantly faster growth of primary pancreatic tumors and a higher incidence of lymph-node metastasis occurred in NOG mice compared to nude mice.

CONCLUSION:

RFP-expressing tumor stroma, which traffics together with cancer cells to lymph nodes, is useful to observe tumor behavior, such as lymph-node metastasis in a PDOX NOG-mouse model which can be used for evaluation of novel anti-metastatic agents, as well as personalized therapy to identify effective drugs.

• Authors: Norihiko Sugisawa, Kentaro Miyake, Takashi Higuchi, Hiromichi Oshiro, Jun Ho Park, Kei Kawaguchi, Michael Bouvet, Michiaki Unno, Robert M Hoffman
• Journal: Anticancer research (Anticancer Res) Vol. 42 Issue 2 Pg. 739-743 (Feb 2022) ISSN: 1791-7530 [Electronic] Greece
• PMID: 35093872 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Luminescent Proteins
• red fluorescent protein

Topics

• Animals
• Disease Models, Animal
• Humans
• Intravital Microscopy
• Luminescent Proteins (metabolism)
• Lymphatic Metastasis
• Mice
• Mice, Nude
• Mice, SCID
• Mice, Transgenic
• Neoplasm Transplantation
• Pancreatic Neoplasms (metabolism, pathology)