Immunohistochemical Expression and Serum Levels of CD44 as Prognostic Indicators in Patients with Non-Small Cell Lung Cancer

Shinohara, Shinji; Hanagiri, Takeshi; Taira, Akihiro; Takenaka, Masaru; Oka, Shiro; Chikaishi, Yasuhiro; Uramoto, Hidetaka; Saito, Tomoko; Yamada, Sohsuke; Tanaka, Fumihiro

doi:10.1159/000445951

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…High expression of CD44 was also reported to be associated with not only occurrence and migration ( 15 ) but also metastasis ( 24 ) and drug resistance ( 19 ) of NSCLC. In the present study, an association between a higher CD44-positive expression rate and higher T stage was observed in NSCLC, which was consistent with the report from Shinohara et al ( 14 ) where significant associations were observed between CD44 expression and clinicopathological factors including T stage, N stage, pathological stage and histological type following immunohistochemical analysis of a cohort consisting of 261 consecutive patients ( 12 ), but the present study failed to identify a significant association between CD44 expression and occurrence or metastasis. This may be due to the small cohort in the present study, so a future study with a large cohort is still required to confirm the association between CD44 expression and other clinicopathological prognosis factors.…”

Section: Discussionsupporting

confidence: 94%

“…In previous studies, high expression of CD44 was hypothesized to be associated with poor prognosis in NSCLC ( 14 , 23 ). High expression of CD44 was also reported to be associated with not only occurrence and migration ( 15 ) but also metastasis ( 24 ) and drug resistance ( 19 ) of NSCLC.…”

Section: Discussionmentioning

confidence: 95%

“…In lung cancer, diverse studies have clarified that the expression of CD44 is associated with tumorigenesis and malignant features of NSCLC ( 11 , 12 ). Tumor and serum expression of CD44 have been confirmed as prognostic indicators for patients with NSCLC ( 13 , 14 ). In addition, overexpression of CD44 is associated with the occurrence and migration of NSCLC ( 15 ).…”

Section: Introductionmentioning

confidence: 98%

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CD44 promotes cell proliferation in non-small cell lung cancer

Yang

et al. 2018

Oncol Lett

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Cluster of differentiation 44 (CD44), a marker for cancer stem cells, has been reported to be associated with poor prognosis in non-small cell lung cancer (NSCLC), but its involvement in tumor growth has not fully been elucidated. The present study explored the associations between CD44 expression and clinicopathological features using immunohistochemistry in 94 NSCLC cases, as well as proliferation in cells with aberrant expression of this protein. Overexpression of CD44 was achieved by transfecting H1299 cells with CD44 expression vectors, and inhibition of CD44 expression was performed by transfecting small interfering RNAs into A549 cells. Cell proliferation was measured using Cell Counting Kit-8 assays and flat plate colony formation assay was performed to confirm the cellular anchorage growth in vitro. In total, 64 (68.1%) of the 94 NSCLC cases stained positive for CD44 expression. High expression of CD44 was associated with advanced T stage in NSCLC. Overexpression of CD44 in H1299 cells promoted cell proliferation and colony formation in vitro. Meanwhile, knockdown of CD44 expression in A549 cells suppressed cell proliferation and colony formation in vitro. High expression of CD44 may promote NSCLC progression by increasing cancer cell proliferation; therefore, it may serve as a potential biomarker for diagnosis or target therapy.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

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CD44 promotes cell proliferation in non-small cell lung cancer

Yang

et al. 2018

Oncol Lett

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“…The expression of CD44 in metastatic ovarian cancer cells was significantly higher than that in primary ovarian cancer cells [28]. CD44 has been shown to be associated with tumor migration and metastasis in colon cancer and breast cancers，and could be used as a prognostic indicator in lung cancer [29][30][31]. CD44 is the major cellular receptor for HA and in association with HA, CD44 has a certain impact on the activation of cell-survival antiapoptotic proteins, consequently resulting in tumor cell proliferation and tumorigenesis in hepatocellular carcinoma and lung cancers [6,32,33].…”

Section: Discussionmentioning

confidence: 99%

Targeting CD44 by CRISPR-Cas9 in Multi-Drug Resistant Osteosarcoma Cells

Zheng

Wan

Nur

et al. 2018

Cell Physiol Biochem

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Background/Aims: Drug resistance is the main difficulty for the current treatment for osteosarcoma. Cluster of differentiation 44 (CD44) is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression, metastasis and drug resistance. In this study, we aimed to determine the effects of CD44 on migration, invasion, proliferation, and the drug-sensitivity of osteosarcoma. Methods: 96 human osteosarcoma tissues from 56 patients were collected to evaluate the expression of CD44 in osteosarcoma tissue by immunohistochemistry. CRISPR-Cas9 system was used to specifically silence CD44 in drug-resistant cell lines (KHOSR2 and U-2OSR2). The migration and invasion activities of cells was demonstrated by wound healing and transwell invasion assay. The proliferation speed of the cells was detected under 3D cell culture condition. Drug resistance of cells was detected by MTT and drug uptake assay. Results: The immunohistochemistry results demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis, recurrence and drug resistance in patients with osteosarcoma. After knocking-out of CD44 by the CRISPR-Cas9 system, not only the migration and invasion activities of osteosarcoma cells were significantly inhibited, but the drug sensitivity was also enhanced. Conclusion: CD44 silencing could inhibit the development of osteosarcoma migration, invasion, proliferation and ameliorate drug resistance to current treatment in osteosarcoma. This study applies new strategy to target CD44, which may improve the prognosis of osteosarcoma.

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“…Understanding of molecular markers of cancer stem cells in NPC can improve the development of clinical strategies, as seen in inhibition of tumor growth by interference with CD44v6 signaling [49] and a specific ALDH1A1 inhibitor for cancer stem cell target therapy [50]. In addition, higher serum CD44v6 levels in lung cancer [51] and joint detection of CD44v6 and CD62P in NPC peripheral blood were found to be significantly unfavorable prognostic factors. Therefore, further studies are needed to apply cancer stem cell markers for therapeutic targets and biomarkers in NPC.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-Related DNA Damage and Cancer Stem Cell Markers in Nasopharyngeal Carcinoma

Wang

Zhao

et al. 2016

Mediators of Inflammation

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Nitrative and oxidative DNA damage plays an important role in inflammation-related carcinogenesis. To investigate the involvement of stem cells in Epstein-Barr virus infection-related nasopharyngeal carcinoma (NPC), we used double immunofluorescence staining to examine several cancer stem/progenitor cell markers (CD44v6, CD24, and ALDH1A1) in NPC tissues and NPC cell lines. We also measured 8-nitroguanine formation as an indicator of inflammation-related DNA lesions. The staining intensity of 8-nitroguanine was significantly higher in cancer cells and inflammatory cells in the stroma of NPC tissues than in chronic nasopharyngitis tissues. Expression levels of CD44v6 and ALDH1A1 were significantly increased in cancer cells of primary NPC specimens in comparison to chronic nasopharyngitis tissues. Similarly, more intense staining of CD44v6 and ALDH1A1 was detected in an NPC cell line than in an immortalized nasopharyngeal epithelial cell line. In the case of CD24 staining, there was no significant difference between NPC and chronic nasopharyngitis tissues. 8-Nitroguanine was detected in both CD44v6- and ALDH1A1-positive stem cells in NPC tissues. In conclusion, CD44v6 and ALDH1A1 are candidate stem cell markers for NPC, and the increased formation of DNA lesions by inflammation may result in the mutation of stem cells, leading to tumor development in NPC.

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Immunohistochemical Expression and Serum Levels of CD44 as Prognostic Indicators in Patients with Non-Small Cell Lung Cancer

Cited by 14 publications

References 34 publications

CD44 promotes cell proliferation in non-small cell lung cancer

CD44 promotes cell proliferation in non-small cell lung cancer

Targeting CD44 by CRISPR-Cas9 in Multi-Drug Resistant Osteosarcoma Cells

Inflammation-Related DNA Damage and Cancer Stem Cell Markers in Nasopharyngeal Carcinoma

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