Folate receptor-α (FOLR1) expression and function in triple negative tumors

Brian M. Necela, Jennifer A. Crozier, Cathy A. Andorfer, Laura Lewis-Tuffin, Jennifer M. Kachergus, Xochiquetzal J. Geiger, Krishna R Kalari, Daniel J. Serie, Zhifu D Sun, Alvaro Moreno Aspita, Daniel J. O'Shannessy, Julia D. Maltzman, Ann E. McCullough, Barbara A Pockaj, Heather E. Cunliffe, Karla V. Ballman, E Aubrey Thompson, Edith A. Perez

Research output: Contribution to journalArticle

Abstract

Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense overexpression of FOLR1 in breast tumors and poor prognosis, yet there is limited examination of the distribution of FOLR1 across clinically relevant breast cancer subtypes. To explore this further, we used RNA-seq data from multiple patient cohorts to analyze the distribution of FOLR1 mRNA across breast cancer subtypes comprised of estrogen receptor positive (ER+), human epidermal growth factor receptor positive (HER2+), and triple negative (TNBC) tumors. FOLR1 expression varied within breast tumor subtypes; triple negative/basal tumors were significantly associated with increased expression of FOLR1 mRNA, compared to ER+ and HER2+ tumors. However, subsets of high level FOLR1 expressing tumors were observed in all clinical subtypes. These observations were supported by immunohistochemical analysis of tissue microarrays, with the largest number of 3+ positive tumors and highest H-scores of any subtype represented by triple negatives, and lowest by ER+ tumors. FOLR1 expression did not correlate to common clinicopathological parameters such as tumor stage and nodal status. To delineate the importance of FOLR1 overexpression in triple negative cancers, RNA-interference was used to deplete FOLR1 in overexpressing triple negative cell breast lines. Loss of FOLR1 resulted in growth inhibition, whereas FOLR1 overexpression promoted folate uptake and growth advantage in low folate conditions. Taken together, our data suggests patients with triple negative cancers expressing high FOLR1 expression represent an important population of patients that may benefit from targeted anti-FOLR1 therapy. This may prove particularly helpful for a large number of patients who would typically be classified as triple negative and who to this point have been left without any targeted treatment options.

Original languageEnglish (US)
Article numbere0122209
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 27 2015

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Folic Acid
folic acid
Tumors
receptors
neoplasms
Neoplasms
breast neoplasms
Breast Neoplasms
Folate Receptor 1
RNA
Tissue Array Analysis
Messenger RNA
therapeutics
tissue analysis
Microarrays
Epidermal Growth Factor Receptor
Estrogen Receptors
Growth
RNA Interference
RNA interference

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Necela, B. M., Crozier, J. A., Andorfer, C. A., Lewis-Tuffin, L., Kachergus, J. M., Geiger, X. J., ... Perez, E. A. (2015). Folate receptor-α (FOLR1) expression and function in triple negative tumors. PLoS One, 10(3), [e0122209]. https://doi.org/10.1371/journal.pone.0122209

Folate receptor-α (FOLR1) expression and function in triple negative tumors. / Necela, Brian M.; Crozier, Jennifer A.; Andorfer, Cathy A.; Lewis-Tuffin, Laura; Kachergus, Jennifer M.; Geiger, Xochiquetzal J.; Kalari, Krishna R; Serie, Daniel J.; Sun, Zhifu D; Aspita, Alvaro Moreno; O'Shannessy, Daniel J.; Maltzman, Julia D.; McCullough, Ann E.; Pockaj, Barbara A; Cunliffe, Heather E.; Ballman, Karla V.; Thompson, E Aubrey; Perez, Edith A.

In: PLoS One, Vol. 10, No. 3, e0122209, 27.03.2015.

Research output: Contribution to journalArticle

Necela, BM, Crozier, JA, Andorfer, CA, Lewis-Tuffin, L, Kachergus, JM, Geiger, XJ, Kalari, KR, Serie, DJ, Sun, ZD, Aspita, AM, O'Shannessy, DJ, Maltzman, JD, McCullough, AE, Pockaj, BA, Cunliffe, HE, Ballman, KV, Thompson, EA & Perez, EA 2015, 'Folate receptor-α (FOLR1) expression and function in triple negative tumors', PLoS One, vol. 10, no. 3, e0122209. https://doi.org/10.1371/journal.pone.0122209
Necela BM, Crozier JA, Andorfer CA, Lewis-Tuffin L, Kachergus JM, Geiger XJ et al. Folate receptor-α (FOLR1) expression and function in triple negative tumors. PLoS One. 2015 Mar 27;10(3). e0122209. https://doi.org/10.1371/journal.pone.0122209
Necela, Brian M. ; Crozier, Jennifer A. ; Andorfer, Cathy A. ; Lewis-Tuffin, Laura ; Kachergus, Jennifer M. ; Geiger, Xochiquetzal J. ; Kalari, Krishna R ; Serie, Daniel J. ; Sun, Zhifu D ; Aspita, Alvaro Moreno ; O'Shannessy, Daniel J. ; Maltzman, Julia D. ; McCullough, Ann E. ; Pockaj, Barbara A ; Cunliffe, Heather E. ; Ballman, Karla V. ; Thompson, E Aubrey ; Perez, Edith A. / Folate receptor-α (FOLR1) expression and function in triple negative tumors. In: PLoS One. 2015 ; Vol. 10, No. 3.
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AU - O'Shannessy, Daniel J.

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