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ID 118214
Title Alternative
肺癌における腫瘍浸潤線維細胞の走化因子とその疾患予後に及ぼす影響についての解析
CHEMOTACTIC FACTORS FOR TUMOR-INFILTRATING FIBROCYTES IN LUNG CANCER
Author
Afroj, Tania Tokushima University
Abe, Akane Tokushima University
Keywords
C‑X‑C chemokine receptor type 4
C‑X‑C motif chemokine 12
LUAD
NSCLC
fibrocyte
Content Type
Thesis or Dissertation
Description
Fibrocytes, which are bone marrow‑derived collagen‑producing cells, have been reported to be involved in pathogenesis of pulmonary fibrosis. Our previous study reported that tumor‑infiltrating fibrocytes play a role in tumor progression and drug resistance in lung cancer. The present study therefore examined chemotactic factors for fibrocytes in tissues of non‑small cell lung cancer (NSCLC) and their prognostic significance. Surgically resected tumor tissues were examined for the expression of chemotactic factors, including C‑X‑C motif chemokine 12 (CXCL12), CCL2, platelet‑derived growth factor (PDGF)‑AA and PDGF‑BB, as well as tumor‑infiltrating fibrocytes by immunostaining. The chemotactic ability of fibrocytes in response to each factor was evaluated using a migration assay by counting the migrated cells microscopically, and expression of receptors for chemotactic factors were analyzed by flow cytometry. The expression of CXCL12, but not CCL2, PDGF‑AA, or PDGF‑BB, was associated with the number of tumor‑infiltrating fibrocytes in lung adenocarcinoma (LUAD), but not lung squamous cell carcinoma (LUSQ). In addition, patients with an increased expression of CXCL12 in LUAD but not LUSQ showed a significantly poorer prognosis compared with those with a decreased expression. However, the expression of CCL2, PDGF‑AA and PDGF‑BB was not correlated with the prognosis of patients with NSCLC. The number of fibrocytes was associated with a poor prognosis in LUAD. Fibrocytes derived from the peripheral blood of healthy subjects as well as patients with lung cancer expressed higher levels of CXCR4 compared with CCR2, PDGF and receptor‑α and receptor‑β. Overall, these results suggested that targeting tumor‑infiltrating fibrocytes via the CXCL12/CXCR4 axis may be a useful strategy for controlling the progression of NSCLC, particularly LUAD.
Journal Title
Oncology Letters
ISSN
17921074
17921082
Publisher
Spandidos Publications
Volume
24
Issue
5
Start Page
417
Published Date
2022-09-30
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Makoto Tobiumeの学位論文として提出され,学位審査・授与の対象となっている。
Rights
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.( https://creativecommons.org/licenses/by-nc-nd/4.0/ )
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3677号
Diploma Number
甲医第1561号
Granted Date
2023-02-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences