Ameloblastoma is a benign tumor of the odontogenic epithelium with several histological subtypes. All subtypes of ameloblastoma contain abundant stroma; the tumor cells invade collectively into the surrounding tissues without losing intratumor cell attachments. However, the molecular mechanisms mediating ameloblastoma invasion remain unclear. Here, we evaluated the functional significance of the interactions between ameloblastoma tumor cells and stromal fibroblasts on collective cellular invasion using a three‐dimensional cultivation method, double‐layered collagen gel hemisphere (
DL
‐
CGH
) culture. The
AM
‐1 plexiform and
AM
‐3 follicular human ameloblastoma cell lines and
HFF
‐2 human fibroblasts were labeled with GFP and DsRed, respectively. Collective cellular invasion of ameloblastoma cells was assessed in the presence or absence of fibroblasts. Notably, without fibroblasts,
AM
‐1 cells formed sharp, plexiform‐like invasive processes, whereas
AM
‐3 cells formed a series of blunt processes often observed during collective migration. In comparison, under the cocultures with
HFF
‐2 fibroblasts,
AM
‐3 cells formed tuft‐like invasive processes and collectively invaded into outer layer more than that observed with
AM
‐1 cells. Moreover,
HFF
‐2 fibroblasts localized to the tips of the invasive tumor processes. These findings suggest that tumor‐associated cells assist tumor cell invasion. Microscopic analysis of sectioned three‐dimensional cultures revealed that
AM
‐3/
HFF
‐2 hemispheres were histologically similar to follicular ameloblastoma tumor samples. Therefore, our findings suggest that ameloblastoma subtypes exhibit distinct invasion patterns and that fibroblasts promote collective tumor invasion in follicular ameloblastoma.
Ameloblastoma is benign odontogenic tumours that mainly occur in the jawbone. This tumour induces aggressive invasion into the surrounding bone and has a high recurrence rate after surgery. Therefore, mandibular resection is performed in many patients with this tumour, causing aesthetic and functional problems. It is necessary to develop a novel treatment strategy for ameloblastoma, but there are currently no innovative treatments. Although our understanding of the molecular biological mechanisms of ameloblastoma is still insufficient, there have been many recent reports of new molecular biological findings on ameloblastoma. Therefore, bioactive factors that have potential for novel therapeutic methods, such as molecular targeted therapy, have been discovered in ameloblastoma. In this review, we summarize the molecular biological findings of ameloblastoma reported over several decades, focusing on factors involved in invasion into surrounding tissues and disease-specific gene mutations. We also mention the effect of the interaction between tumour cells and stromal components in ameloblastoma on tumour development.
Scientific field of dental Science:
Oral surgery, Odontogenic tumor, Ameloblastoma.
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