Serum levels of surfactant protein D predict the anti-tumor activity of gefitinib in patients with advanced non-small cell lung cancer

Yamaguchi, Hiroyuki; Soda, Hiroshi; Nakamura, Yoichi; Takasu, Mineyo; Tomonaga, Nanae; Nakano, Hirofumi; Doi, Seiji; Nakatomi, Katsumi; Nagashima, Seiji; Takatani, Hiroshi; Fukuda, Minoru; Hayashi, Tomayoshi; Tsukamoto, Kazuhiro; Kohno, Shigeru

doi:10.1007/s00280-010-1325-x

Cited by 15 publications

(7 citation statements)

References 32 publications

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“…Furthermore, it is noteworthy that PFL enhanced the susceptibility of cancer cells to anti-cancer drugs such as gefitinib. Serum levels of surfactant protein D (SP-D), a C-type lectin with innate immune functions, also reportedly are associated with gefitinib efficacy [ 31 ]. Therefore, future work will be directed toward evaluating the in vivo adjuvant effect of PFL with various anti-cancer drugs to increase therapeutic efficacy and reduce side effects.…”

Section: Discussionmentioning

confidence: 99%

High mannose-binding Pseudomonas fluorescens lectin (PFL) downregulates cell surface integrin/EGFR and induces autophagy in gastric cancer cells

et al. 2016

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BackgroundPseudomonas fluorescens lectin (PFL) belongs to a recently discovered anti-HIV lectin family and induces anoikis-like cell death of MKN28 gastric cancer cells by causing α2 integrin internalization through recognition of high mannose glycans; however, the detailed anti-cancer mechanism is not fully elucidated.MethodsCell adherence potency of MKN28 upon PFL treatment was assessed using a colorimetric assay. Cell surface molecules to which PFL bound were identified by peptide mass finger printing with Matrix Assisted Laser Desorption/Ionization-time of flight mass spectrometry and their cellular localization determined by immunofluorescence microscopy. Gene and protein expression in PFL-treated MKN28 cells were evaluated by microarray analysis and western blot, and the function of these genes was evaluated by siRNA knock-down. A proliferation assay measured the sensitivity of PFL-treated cancer cells to anti-cancer drugs. The effect of PFL on subcutaneous MKN28 tumor growth and hepatic tumor formation in BALB/c nude mice was evaluated.ResultsThe strength of MKN28 cell adherence in vitro to the extracellular matrix was impaired by PFL treatment, consistent with the observation that PFL induces rapid downregulation of surface integrins. PFL also was found to bind to cell surface epidermal growth factor receptor (EGFR). Surface EGFR molecules were endocytosed following PFL binding, and were degraded in a time-dependent fashion. This degradation process was largely the result of autophagy, as revealed by the increased expression of autophagic proteins. PFL-induced EGFR degradation was partly inhibited by RAB7 siRNA as well as LC3 siRNA, and internalized EGFR colocalized with ATG9 at 48 h post-PFL treatment, suggesting that these proteins contribute to dynamic degradation induced by PFL. PFL-induced decrease in surface EGFR rendered MKN28 cells susceptible to gefitinib, a selective inhibitor of EGFR tyrosine kinase. In vivo experiments showed that PFL-treated MKN28-EGFP cells injected in the portal vein of BALB/c nude mice failed to form tumor colonies on the liver, and intratumoral injection of PFL significantly inhibited tumor growth.ConclusionPFL-mediated downregulation of integrin and EGFR contributes to the inhibition of tumor growth in vitro and in vivo. This novel anti-cancer mechanism of PFL suggests that this lectin would be useful as an anti-cancer drug or an adjuvant for other drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2099-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

High mannose-binding Pseudomonas fluorescens lectin (PFL) downregulates cell surface integrin/EGFR and induces autophagy in gastric cancer cells

et al. 2016

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“…Although initially discovered from the lung where it is secreted by type II and Clara cells [4], extra-pulmonary existence of SP-D has also been reported [5]. It also has been proposed to be a useful biomarker in certain carcinomas [6,7] and a range of lung-associated diseases [7,8]. Involvement of SP-D in immunosurveillance and immunomodulation is well documented in pulmonary allergy and asthma.…”

Section: Introductionmentioning

confidence: 99%

Human Surfactant Protein D Alters Oxidative Stress and HMGA1 Expression to Induce p53 Apoptotic Pathway in Eosinophil Leukemic Cell Line

et al. 2013

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Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and time-dependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2) showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SP-D in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host’s immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.

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“…HLA-DRB5 has also been considered a possible prognostic factor for gastric cancer ( Hang et al, 2018 ). High expression of SFTPD might function to prevent progression of lung cancer ( Yamaguchi et al, 2011 ). Increased SFTPD levels have been shown to be associated with fewer distant metastases and progression-free survival in LUAD that harbors EGFR mutations ( Umeda et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A Nomogram Integrating Ferroptosis- and Immune-Related Biomarkers for Prediction of Overall Survival in Lung Adenocarcinoma

Chai

Zhang

et al. 2021

Front. Genet.

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Ferroptosis plays a dual role in cancer, which is known to be affected to antitumor immune responses. However, the association between ferroptosis and antitumor immune responses is uncertain in lung adenocarcinoma (LUAD). In this work, 38 ferroptosis-related genes (FRGs) and 429 immune-related genes (IRGs) were identified as being differentially expressed between tumor and normal samples. Two risk score formulas consisting of seven FRGs and four IRGs, respectively, were developed by Lasso-penalized Cox regression and verified in the GSE13213 dataset. The CIBERSORT algorithm was used to estimate the relative abundance of immune cells in tumors. The correlation between FRGs and immune cells was evaluated using the TIMER database. The results indicated that the development of ferroptosis was synergistic with that of anti-tumor immunity in LUAD. The concordance index and calibration curves showed that the performance of a nomogram that combines clinical staging and risk scores is superior to that of models using a single prognostic factor. In conclusion, ferroptosis might be synergistic with anti-tumor immunity in LUAD. The combined nomogram could reliably predict the probability of overall survival of LUAD patients. These findings may be useful for future investigation of prognostic value and therapeutic potential related to ferroptosis and tumor immunity in LUAD.

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Serum levels of surfactant protein D predict the anti-tumor activity of gefitinib in patients with advanced non-small cell lung cancer

Cited by 15 publications

References 32 publications

High mannose-binding Pseudomonas fluorescens lectin (PFL) downregulates cell surface integrin/EGFR and induces autophagy in gastric cancer cells

High mannose-binding Pseudomonas fluorescens lectin (PFL) downregulates cell surface integrin/EGFR and induces autophagy in gastric cancer cells

Human Surfactant Protein D Alters Oxidative Stress and HMGA1 Expression to Induce p53 Apoptotic Pathway in Eosinophil Leukemic Cell Line

A Nomogram Integrating Ferroptosis- and Immune-Related Biomarkers for Prediction of Overall Survival in Lung Adenocarcinoma

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