Fascin is involved in cancer cell invasion and is regulated by stromal factors

Abstract

The tumor microenvironment plays an important role in cancer growth, invasion and metastasis. The stroma surrounding a tumor is known to contain a variety of factors that can increase angiogenesis, cancer growth and tumor progression. The aim of the present study was to determine the role of fascin in cancer growth and invasion and identify stromal factors involved in cancer progression. A fascin-depleted cell line (fascin dep ) was used to observe the role of fascin in cancer invasion. Compared with wild-type Mock cells, cancer cell invasion in Matrigel-coated Transwell and three-dimensional (3D) culture system were reduced by fascin depletion. Tumor cell growth in vivo was also significantly reduced in mice injected with fascin dep cells. Notably, fascin expression was increased during Transwell invasion with Matrigel compared to Transwell invasion without Matrigel. TGF-β1, EGF and IL-1β significantly stimulated fascin expression. Such increased expression of fascin was also observed in cultured cells using conditioned media (CM) from cancer-associated fibroblasts (CAFs). However, no significant change in fascin expression was observed using CM from normal fibroblasts (NFs). Stimulated expression of fascin by Matrigel and CAFs was reduced by biological specific inhibitor of TGF-β1, EGF and IL-1β. Compared with wild-type Mock cells, the fascin dep cell line showed low RhoA and NF-κB activity, suggesting that RhoA and NF-κB signals are involved in fascin expression. In conclusion, stromal factors are involved in cancer invasion and progression by activating intracellular signaling of cancer cells to increase fascin expression. Fascin is involved in cancer cell invasion and is regulated by stromal factors

Cancer‑associated fibroblast stimulates cancer cell invasion in an interleukin‑1 receptor (IL‑1R)‑dependent manner

“…1, recombinant IL-1β treatment incresed invasion 2.75-fold compared to the control. To investigate the expression of IL-1β in the tumor, we used a xenofrafted tongue tumor specimen established in our previous experiments (8). IL-1β expression was located in the cytoplasm of the cancer cells and cancer-associate fibroblasts.…”

“…The xenograft tumor tissue was used to observe the expression of IL-1β. Tumor xenograft was established by implatation of OSCC cells in athymic nude mouse in our previous study (8). Briefly, OSCC cells were injected into mouse tongue and growth of tumor xenografts was observed for 5 weeks.…”

Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?

“…139 Signal transducer and activator of transcription 3 (STAT3) and nuclear factor kB (NF-kB) are two well-known TFs required for the cytokine-induced expression of FSCN1 in human cancer cells. [140][141][142][143][144] FSCN1 expression is induced by a variety of cytokines, such as IL-6, tumor necrosis factor (TNF)-a, and oncostatin M (OSM). These cytokines activate STAT3 and NF-kB in human breast and gastric cancer cells to induce the expression.…”

Features of fascin expression in the small intestine of rats exposed to processed Eucheuma seaweed

“…It is believed that fascin overexpression is a subject to an inflammation-mediated regulation. It has been reported that inflammation-related cytokines such as tumor necrosis factoralpha (TNF-α), IL-1β and transforming growth factor-beta (TGF-β) may upregulate fascin [27,28]. Thus, it can be assumed that E407a-induced tissue damage and destruction resulted in the development of inflammation and subsequent overexpression of fascin in the most damaged areas due to the pro-inflammatory microenvironment.…”