TY - JOUR
T1 - Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral Neuropathy
AU - Staff, Nathan P.
AU - Hrstka, Sybil C.
AU - Dasari, Surendra
AU - Capobianco, Enrico
AU - Rieger, Sandra
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/8
Y1 - 2023/8
N2 - The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN.
AB - The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN.
KW - CIPN
KW - MMP-13
KW - Taxol
KW - chemotherapy-induced peripheral neuropathy
KW - collagen
KW - extracellular matrix
KW - matrix metalloproteinase
KW - paclitaxel
KW - skin
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U2 - 10.3390/cancers15164191
DO - 10.3390/cancers15164191
M3 - Article
AN - SCOPUS:85168921113
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 16
M1 - 4191
ER -