Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle

Haslam, Iain S.; El-Chami, Cecile; Faruqi, H; Shahmalak, Asim; O’Neill, CA; Paus, Ralf

doi:10.1111/bjd.13549

Cited by 33 publications

(48 citation statements)

References 58 publications

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“…3 Of note, ABCG2 inhibition enhanced nuclear staining of Hoechst 33342 dye, supporting key functional roles of these transporters in the maintenance of hair follicle cell components including epithelial stem cells. 3 At first glance, the significance of the current paper may not be fully appreciated. The listed transporter names would be hardly distinguishable, which could make the article somewhat puzzling to go through.…”

Section: Original Article P 1562mentioning

confidence: 84%

“…1,2 Despite the biological significance and intrinsic expression of ABC transporters, their roles in the skin, especially in the hair follicle, have been insufficiently investigated. 3 In this issue of the BJD, Haslam et al 3 demonstrate that a variety of ABC transporters are differentially expressed in human hair follicles. Intriguingly, the expression of ABCG2 was restricted primarily to the bulge area harbouring epithelial stem cells, while the distribution of other subtypes, such as ABCA1, ABCB1, ABCC1, ABCA4, ABCC4 and ABCA1, was less restricted.…”

Section: Original Article P 1562mentioning

confidence: 99%

“…Intriguingly, the expression of ABCG2 was restricted primarily to the bulge area harbouring epithelial stem cells, while the distribution of other subtypes, such as ABCA1, ABCB1, ABCC1, ABCA4, ABCC4 and ABCA1, was less restricted. 3 In addition, adopting a human hair follicle organ culture model and using a substrate dye, they successfully showed that the blockade of transporters resulted in dye accumulation in follicular keratinocytes. 3 Of note, ABCG2 inhibition enhanced nuclear staining of Hoechst 33342 dye, supporting key functional roles of these transporters in the maintenance of hair follicle cell components including epithelial stem cells.…”

Section: Original Article P 1562mentioning

confidence: 99%

“…3 In addition, adopting a human hair follicle organ culture model and using a substrate dye, they successfully showed that the blockade of transporters resulted in dye accumulation in follicular keratinocytes. 3 Of note, ABCG2 inhibition enhanced nuclear staining of Hoechst 33342 dye, supporting key functional roles of these transporters in the maintenance of hair follicle cell components including epithelial stem cells. 3 At first glance, the significance of the current paper may not be fully appreciated.…”

Section: Original Article P 1562mentioning

confidence: 99%

“…3 As the authors mention, a well-known application of specific inhibition of ABC transporters is the isolation of side-population (SP) cells, a putative stem cell population, from living tissue. 4,5 SP cells express high levels of ABCB1 and ABCG2 and are capable of excluding a dye, in this case Hoechst 33342.…”

Section: Original Article P 1562mentioning

confidence: 99%

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Pump up the hair follicle

Ohyama

2015

Br J Dermatol

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References 1 Fauconneau A, Pham-Ledard A, Cappellen D et al. Assessment of diagnostic criteria between primary cutaneous anaplastic large-cell lymphoma and CD30-rich transformed mycosis fungoides; a study of 66 cases. Br J Dermatol 2015; 172:1547-54. 2 Hsi AC, Lee SJ, Rosman IS et al. Expression of helper T cell master regulators in inflammatory dermatoses and primary cutaneous T-cell lymphomas: diagnostic implications. J Am Acad Dermatol 2015; 72:159-67. 3 Guitart J, Martinez-Escala ME, Deonizio JM et al. CD30 + cutaneous lymphoproliferative disorders with pseudocarcinomatous hyperplasia are associated with a T-helper-17 cytokine profile and infiltrating granulocytes. J Am Acad Dermatol 2015; 72:508-15. 4 Benner MF, Ballabio E, van Kester MS et al. Primary cutaneous anaplastic large cell lymphoma shows a distinct miRNA expression profile and reveals differences from tumor-stage mycosis fungoides. Exp Dermatol 2012; 21:632-4. 5 Moyal L, Barzilai A, Gorovitz B et al. miR-155 is involved in tumor progression of mycosis fungoides. Exp Dermatol 2013; 22:431-3. 6 Sandoval J, D ıaz-Lagares A, Salgado R et al. MicroRNA expression profiling and DNA methylation signature for deregulated microR-NA in cutaneous T-cell lymphoma. J Invest Dermal 2015; 135: 1128-37.

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Section: Original Article P 1562mentioning

confidence: 84%

Section: Original Article P 1562mentioning

confidence: 99%

Section: Original Article P 1562mentioning

confidence: 99%

Section: Original Article P 1562mentioning

confidence: 99%

Section: Original Article P 1562mentioning

confidence: 99%

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Pump up the hair follicle

Ohyama

2015

Br J Dermatol

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Insights Into the Biology of Persistent Chemotherapy-Induced Alopecia via Genomic Approaches—An Avenue to Clinical Translation?

2020

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A major concern among patients with cancer is hair loss secondary to chemotherapy, an adverse effect that occurs among approximately 65% of patients who undergo this form of therapy. 1 The association between chemotherapy and hair loss is well known across society, and chemotherapy-induced alopecia (CIA) can, therefore, induce a sense of violated privacy, or even shame, among those affected. The association of this adverse effect with reduced self-esteem, social confidence, and sexuality is particularly devastating for women. The anticipation of CIA is so distressing that some female patients even seriously consider refusing chemotherapy treatment. 2 A large proportion of chemotherapeutic agents act by targeting specific phases of the cell division process and are thus highly effective in terms of killing rapidly dividing cancer cells. However, the antimitotic assault of these agents also affects other continuously dividing cell types, including the hair matrix keratinocytes, which display intense mitotic activity for continuous hair growth.Until recently, CIA was considered to be typically reversible, with physicians assuming that hair regrowth would occur between 3 and 6 months after the end of therapy. However, over the years, several reports have described cases of persistent CIA (pCIA), in which incomplete or total absence of hair regrowth has been reported several years after the completion of chemotherapy. 3,4 It is assumed that this particular form of alopecia results from damage to the hair follicle stem cells that are responsible for reinitiating follicle growth. 5 Patients with breast cancer seem to be particularly affected by pCIA. 6 Recent research suggests that up to 50% and 10% of patients who survive breast cancer experience minor and severe forms of pCIA, respectively. [7][8][9] Both the likelihood of developing CIA and its extent are determined by the nature of the treatment regimen (eg, drug

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Association Between ABCB1 Genetic Variants and Persistent Chemotherapy-Induced Alopecia in Women With Breast Cancer

et al. 2020

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IMPORTANCE Persistent chemotherapy-induced alopecia (pCIA) has been recently described in patients with breast cancer and in its most severe form occurs in up to 10% of these patients. Genetic risk factors associated with pCIA have not been adequately explored.OBJECTIVE To identify genetic variants associated with pCIA. DESIGN, SETTING, AND PARTICIPANTSIn this genetic association study, 215 women with breast cancer treated with docetaxel-based chemotherapy with a follow-up of 1.5 to 10 years after the end of the treatment were recruited retrospectively through 3 hospital oncology units across Spain between 2005 and 2018. Severe pCIA was defined as lack of scalp hair recovery (Common Terminology Criteria for Adverse Events, version 3.0, grade 2) 18 months or more after the end of treatment. Patients with grade 2 pCIA were selected as cases, and those with no sign of residual alopecia 12 months after the end of docetaxel treatment were selected as controls. A genome-wide association study in a discovery phase was conducted, and logistic regression was used to identify variants associated with the risk to develop this adverse effect. The validity of the association was addressed through a replication phase. EXPOSURES Docetaxel-based chemotherapy.MAIN OUTCOMES AND MEASURES Genotypes of single-nucleotide variants associated with pCIA. RESULTSIn total, 215 women with breast cancer (median age, 51.6 years; interquartile range, 44-60 years) were recruited (173 patients for the discovery phase and 42 patients for the replication phase). In the discovery phase, ABCB1 genetic variants were associated with risk to develop pCIA. In particular, single-nucleotide variation rs1202179, a regulatory variant located in an enhancer element that interacts with the ABCB1 promoter, was associated with the occurrence of pCIA. This finding was validated in the replication cohort (combined odds ratio, 4.05; 95% CI, ). This variant is associated with ABCB1 mRNA expression, and the risk allele was associated with decreased ABCB1 expression levels (P = 1.64 × 10 −20 ).CONCLUSIONS AND RELEVANCE This is the first study, to our knowledge, that identifies an association between a regulatory variant in the ABCB1 gene and the occurrence of pCIA in patients with breast cancer who were treated with docetaxel-based therapies. This finding suggests an important insight into the biological mechanisms underlying pCIA and opens the opportunity to explore personalized treatment of these patients.

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Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle

Cited by 33 publications

References 58 publications

Pump up the hair follicle

Pump up the hair follicle

Insights Into the Biology of Persistent Chemotherapy-Induced Alopecia via Genomic Approaches—An Avenue to Clinical Translation?

Association Between ABCB1 Genetic Variants and Persistent Chemotherapy-Induced Alopecia in Women With Breast Cancer

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