Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

Kunyoo Shin, Agnes Lim, Justin I. Odegaard, Jared D. Honeycutt, Sally Kawano, Michael H. Hsieh, Philip A. Beachy

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
JournalNature Cell Biology
Volume16
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Urinary Bladder
Carcinoma
Neoplasms
Urothelium
Neoplastic Stem Cells
Urinary Bladder Neoplasms
Chemical Models
Muscles
Carcinoma in Situ
Carcinogenesis
Stem Cells
Phenotype

ASJC Scopus subject areas

  • Cell Biology

Cite this

Shin, K., Lim, A., Odegaard, J. I., Honeycutt, J. D., Kawano, S., Hsieh, M. H., & Beachy, P. A. (2014). Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. Nature Cell Biology, 16(5), 469-478. https://doi.org/10.1038/ncb2956

Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. / Shin, Kunyoo; Lim, Agnes; Odegaard, Justin I.; Honeycutt, Jared D.; Kawano, Sally; Hsieh, Michael H.; Beachy, Philip A.

In: Nature Cell Biology, Vol. 16, No. 5, 2014, p. 469-478.

Research output: Contribution to journalArticle

Shin, K, Lim, A, Odegaard, JI, Honeycutt, JD, Kawano, S, Hsieh, MH & Beachy, PA 2014, 'Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma', Nature Cell Biology, vol. 16, no. 5, pp. 469-478. https://doi.org/10.1038/ncb2956
Shin, Kunyoo ; Lim, Agnes ; Odegaard, Justin I. ; Honeycutt, Jared D. ; Kawano, Sally ; Hsieh, Michael H. ; Beachy, Philip A. / Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. In: Nature Cell Biology. 2014 ; Vol. 16, No. 5. pp. 469-478.
@article{721da087f6d74e249b384ef93368d30c,
title = "Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma",
abstract = "Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.",
author = "Kunyoo Shin and Agnes Lim and Odegaard, {Justin I.} and Honeycutt, {Jared D.} and Sally Kawano and Hsieh, {Michael H.} and Beachy, {Philip A.}",
year = "2014",
doi = "10.1038/ncb2956",
language = "English (US)",
volume = "16",
pages = "469--478",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

AU - Shin, Kunyoo

AU - Lim, Agnes

AU - Odegaard, Justin I.

AU - Honeycutt, Jared D.

AU - Kawano, Sally

AU - Hsieh, Michael H.

AU - Beachy, Philip A.

PY - 2014

Y1 - 2014

N2 - Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.

AB - Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.

UR - http://www.scopus.com/inward/record.url?scp=84899953445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899953445&partnerID=8YFLogxK

U2 - 10.1038/ncb2956

DO - 10.1038/ncb2956

M3 - Article

VL - 16

SP - 469

EP - 478

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 5

ER -