Recruitment of CD34+ fibroblasts in tumor-associated reactive stroma

The reactive microvasculature hypothesis

Rebeca San Martin, David A. Barron, Jennifer A. Tuxhorn, Steven J. Ressler, Simon W. Hayward, Xiaoyun Shen, Rodolfo Laucirica, Thomas M. Wheeler, Carolina Gutierrez, Gustavo E. Ayala, Michael Ittmann, David R. Rowley

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Reactive stroma co-evolves with cancer, exhibiting tumor-promoting properties. It is also evident at sites of wound repair and fibrosis, playing a key role in tissue homeostasis. The specific cell types of origin and the spatial/temporal patterns of reactive stroma initiation are poorly understood. In this study, we evaluated human tumor tissue arrays by using multiple labeled, quantitative, spectral deconvolution microscopy. We report here a novel CD34/vimentin dual-positive reactive fibroblast that is observed in the cancer microenvironment of human breast, colon, lung, pancreas, thyroid, prostate, and astrocytoma. Recruitment of these cells occurred in xenograft tumors and Matrigel plugs in vivo and was also observed in stromal nodules associated with human benign prostatic hyperplasia. Because spatial and temporal data suggested the microvasculature as a common site of origin for these cells, we analyzed microvasculature fragments in organ culture. Interestingly, fibroblasts with identical phenotypic properties and markers expanded radially from microvasculature explants. We propose the concept of reactive microvasculature for the evolution of reactive stroma at sites of epithelial disruption common in both benign and malignant disorders. Data suggest that the reactive stroma response is conserved among tissues, in normal repair, and in different human cancers. A more clear understanding of the nature and origin of reactive stroma is needed to identify novel therapeutic targets in cancer and fibrosis.

Original languageEnglish (US)
Pages (from-to)1860-1870
Number of pages11
JournalAmerican Journal of Pathology
Volume184
Issue number6
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Microvessels
Neoplasms
Fibrosis
Fibroblasts
Tumor Microenvironment
Organ Culture Techniques
Astrocytoma
Prostatic Hyperplasia
Vimentin
Heterografts
Cancer-Associated Fibroblasts
Prostate
Pancreas
Microscopy
Thyroid Gland
Colon
Breast
Homeostasis
Lung
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

San Martin, R., Barron, D. A., Tuxhorn, J. A., Ressler, S. J., Hayward, S. W., Shen, X., ... Rowley, D. R. (2014). Recruitment of CD34+ fibroblasts in tumor-associated reactive stroma: The reactive microvasculature hypothesis. American Journal of Pathology, 184(6), 1860-1870. https://doi.org/10.1016/j.ajpath.2014.02.021

Recruitment of CD34+ fibroblasts in tumor-associated reactive stroma : The reactive microvasculature hypothesis. / San Martin, Rebeca; Barron, David A.; Tuxhorn, Jennifer A.; Ressler, Steven J.; Hayward, Simon W.; Shen, Xiaoyun; Laucirica, Rodolfo; Wheeler, Thomas M.; Gutierrez, Carolina; Ayala, Gustavo E.; Ittmann, Michael; Rowley, David R.

In: American Journal of Pathology, Vol. 184, No. 6, 01.01.2014, p. 1860-1870.

Research output: Contribution to journalArticle

San Martin, R, Barron, DA, Tuxhorn, JA, Ressler, SJ, Hayward, SW, Shen, X, Laucirica, R, Wheeler, TM, Gutierrez, C, Ayala, GE, Ittmann, M & Rowley, DR 2014, 'Recruitment of CD34+ fibroblasts in tumor-associated reactive stroma: The reactive microvasculature hypothesis', American Journal of Pathology, vol. 184, no. 6, pp. 1860-1870. https://doi.org/10.1016/j.ajpath.2014.02.021
San Martin, Rebeca ; Barron, David A. ; Tuxhorn, Jennifer A. ; Ressler, Steven J. ; Hayward, Simon W. ; Shen, Xiaoyun ; Laucirica, Rodolfo ; Wheeler, Thomas M. ; Gutierrez, Carolina ; Ayala, Gustavo E. ; Ittmann, Michael ; Rowley, David R. / Recruitment of CD34+ fibroblasts in tumor-associated reactive stroma : The reactive microvasculature hypothesis. In: American Journal of Pathology. 2014 ; Vol. 184, No. 6. pp. 1860-1870.
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