Identification of reprogrammed myeloid cell transcriptomes in NSCLC

Research output: Contribution to journalArticle

Anna Durrans, Dingcheng Gao, Ravi Gupta, Kari R. Fischer, Hyejin Choi, Tina El Rayes, Seongho Ryu, Abu Nasar, Cathy F. Spinelli, Weston Andrews, Olivier Elemento, Daniel Nolan, Brendon Stiles, Shahin Rafii, Navneet Narula, Ramana Davuluri, Nasser K. Altorki, Vivek Mittal

Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

Original languageEnglish (US)
Article numbere0129123
JournalPLoS ONE
Volume10
Issue number6
DOIs
StatePublished - Jun 5 2015

PMID: 26046767

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Identification of reprogrammed myeloid cell transcriptomes in NSCLC. / Durrans, Anna; Gao, Dingcheng; Gupta, Ravi; Fischer, Kari R.; Choi, Hyejin; El Rayes, Tina; Ryu, Seongho; Nasar, Abu; Spinelli, Cathy F.; Andrews, Weston; Elemento, Olivier; Nolan, Daniel; Stiles, Brendon; Rafii, Shahin; Narula, Navneet; Davuluri, Ramana; Altorki, Nasser K.; Mittal, Vivek.

In: PLoS ONE, Vol. 10, No. 6, e0129123, 05.06.2015.

Research output: Contribution to journalArticle

Harvard

Durrans, A, Gao, D, Gupta, R, Fischer, KR, Choi, H, El Rayes, T, Ryu, S, Nasar, A, Spinelli, CF, Andrews, W, Elemento, O, Nolan, D, Stiles, B, Rafii, S, Narula, N, Davuluri, R, Altorki, NK & Mittal, V 2015, 'Identification of reprogrammed myeloid cell transcriptomes in NSCLC' PLoS ONE, vol. 10, no. 6, e0129123. https://doi.org/10.1371/journal.pone.0129123

APA

Durrans, A., Gao, D., Gupta, R., Fischer, K. R., Choi, H., El Rayes, T., ... Mittal, V. (2015). Identification of reprogrammed myeloid cell transcriptomes in NSCLC. PLoS ONE, 10(6), [e0129123]. https://doi.org/10.1371/journal.pone.0129123

Vancouver

Durrans A, Gao D, Gupta R, Fischer KR, Choi H, El Rayes T et al. Identification of reprogrammed myeloid cell transcriptomes in NSCLC. PLoS ONE. 2015 Jun 5;10(6). e0129123. https://doi.org/10.1371/journal.pone.0129123

Author

Durrans, Anna ; Gao, Dingcheng ; Gupta, Ravi ; Fischer, Kari R. ; Choi, Hyejin ; El Rayes, Tina ; Ryu, Seongho ; Nasar, Abu ; Spinelli, Cathy F. ; Andrews, Weston ; Elemento, Olivier ; Nolan, Daniel ; Stiles, Brendon ; Rafii, Shahin ; Narula, Navneet ; Davuluri, Ramana ; Altorki, Nasser K. ; Mittal, Vivek. / Identification of reprogrammed myeloid cell transcriptomes in NSCLC. In: PLoS ONE. 2015 ; Vol. 10, No. 6.

BibTeX

@article{04606fbf32824b16a57ac448effd57fa,
title = "Identification of reprogrammed myeloid cell transcriptomes in NSCLC",
abstract = "Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor {"}activated/reprogrammed{"} stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.",
author = "Anna Durrans and Dingcheng Gao and Ravi Gupta and Fischer, {Kari R.} and Hyejin Choi and {El Rayes}, Tina and Seongho Ryu and Abu Nasar and Spinelli, {Cathy F.} and Weston Andrews and Olivier Elemento and Daniel Nolan and Brendon Stiles and Shahin Rafii and Navneet Narula and Ramana Davuluri and Altorki, {Nasser K.} and Vivek Mittal",
year = "2015",
month = "6",
day = "5",
doi = "10.1371/journal.pone.0129123",
language = "English (US)",
volume = "10",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
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}

RIS

TY - JOUR

T1 - Identification of reprogrammed myeloid cell transcriptomes in NSCLC

AU - Durrans, Anna

AU - Gao, Dingcheng

AU - Gupta, Ravi

AU - Fischer, Kari R.

AU - Choi, Hyejin

AU - El Rayes, Tina

AU - Ryu, Seongho

AU - Nasar, Abu

AU - Spinelli, Cathy F.

AU - Andrews, Weston

AU - Elemento, Olivier

AU - Nolan, Daniel

AU - Stiles, Brendon

AU - Rafii, Shahin

AU - Narula, Navneet

AU - Davuluri, Ramana

AU - Altorki, Nasser K.

AU - Mittal, Vivek

PY - 2015/6/5

Y1 - 2015/6/5

N2 - Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

AB - Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

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U2 - 10.1371/journal.pone.0129123

DO - 10.1371/journal.pone.0129123

M3 - Article

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JO - PLoS ONE

T2 - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0129123

ER -

ID: 15166842