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Targeting the Tumor Microenvironment in Cutaneous Squamous Cell Carcinoma

By: Lauren Harrison, MS
Posted: Monday, August 5, 2019

Topical 5-aminolevulinic acid–mediated photodynamic therapy (ALA-PDT) seems to have an inhibitory effect on the activation of cancer-associated fibroblasts, which are components of the tumor microenvironment, and appears to suppress the growth of cutaneous squamous cell carcinoma. Hongwei Wang, PhD, of Fudan University in Shanghai, China, and colleagues published their preclinical research in Photodiagnosis and Photodynamic Therapy.

“[A]ctive fibroblasts could be inactivated and transformed into normal state, providing a new therapeutic direction for immunotherapy of tumors,” concluded the authors.

The team utilized a combination of polymerase chain reactions, Western blot, immunohistochemistry, and cell-migration assays to assess the impact of ALA-PDT on cancer-associated fibroblasts in vitro. Their data showed that co-culture of fibroblasts with tumor cells led to an elevation of alpha-smooth muscle actin and fibroblast activation protein in these fibroblasts. After co-culture, these fibroblasts also had increased migratory ability, suggesting that the tumor cells were able to transform fibroblasts into cancer-associated fibroblasts. Furthermore, when mice were injected with a mixture of tumor cells and fibroblasts, the rate of tumor growth was higher than that in mice injected with tumor cells alone.

The researchers found that treatment of the transformed fibroblasts with ALA-PDT was able to reverse the activation of those fibroblasts. ALA-PDT reduced the expression of alpha smooth muscle actin, fibroblast activation protein, and migratory ability. Additionally, ALA-PDT worked to reverse the activation of cancer-associated fibroblasts in squamous cell carcinoma cells, rendering them normal fibroblasts.

“This research provides preliminary evidence that ALA-PDT can affect [cancer-associated fibroblasts] in the tumor microenvironment,” the authors concluded. “However, the effects of ALA-PDT on the secretory and immune functions of [cancer-associated fibroblasts] are not yet clear and need to be explored in future studies.”

Disclosure: The study authors’ disclosure information may be found at sciencedirect.com.



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