CXCR7 expression correlates with tumor depth in cutaneous squamous cell carcinoma skin lesions and promotes tumor cell survival through ERK activation

We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB+. One fourth of HNSCC cases was human papilloma virus (HPV)− positive, but the TrkB IHC frequency was not different in HPV-positive (HPV+) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV+ HNSCC patients. In HPV− HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis.

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Tumor cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

10.26226/morressier.595a9c59d462b80296ca01a3 ◽

2017 ◽

Author(s):

Pilvi Riihilä

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Cell ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Complement Components

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Cutaneous Squamous Cell Carcinoma (SCC) and the DNA Damage Response: pATM Expression Patterns in Pre-Malignant and Malignant Keratinocyte Skin Lesions

PLoS ONE ◽

10.1371/journal.pone.0021271 ◽

2011 ◽

Vol 6 (7) ◽

pp. e21271 ◽

Cited By ~ 13

Author(s):

Ferina Ismail ◽

Mohamed Ikram ◽

Karin Purdie ◽

Catherine Harwood ◽

Irene Leigh ◽

...

Keyword(s):

Dna Damage ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Dna Damage Response ◽

Squamous Cell ◽

Expression Patterns ◽

Skin Lesions ◽

Cutaneous Squamous Cell Carcinoma ◽

Damage Response

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Abstract 5214: Tumor cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

10.1158/1538-7445.am2018-5214 ◽

2018 ◽

Author(s):

Pilvi Riihilä ◽

Liisa Nissinen ◽

Mehdi Farshchian ◽

Markku Kallajoki ◽

Atte Kivisaari ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Cell ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Complement Components

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Complement Factor D Is a Novel Biomarker and Putative Therapeutic Target in Cutaneous Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers14020305 ◽

2022 ◽

Vol 14 (2) ◽

pp. 305

Author(s):

Pegah Rahmati Nezhad ◽

Pilvi Riihilä ◽

Jaakko S. Knuutila ◽

Kristina Viiklepp ◽

Sirkku Peltonen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Cell ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

Therapeutic Target ◽

Normal Skin ◽

Cutaneous Squamous Cell Carcinoma ◽

Epidermal Keratinocytes ◽

Protein Kinase Activity

Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-γ and interleukin-1β. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression.

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Plasma Treatment Limits Cutaneous Squamous Cell Carcinoma Development In Vitro and In Vivo

Cancers ◽

10.3390/cancers12071993 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1993 ◽

Cited By ~ 2

Author(s):

Gabriella Pasqual-Melo ◽

Thiago Nascimento ◽

Larissa Juliani Sanches ◽

Fernanda Paschoal Blegniski ◽

Julya Karen Bianchi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Plasma Treatment ◽

Cell Carcinoma ◽

Squamous Cell ◽

Healthcare Services ◽

Skin Lesions ◽

Cutaneous Squamous Cell Carcinoma ◽

High Rate

Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo.

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