Y.WONG1, Q.CHEN1, S.NAKAMIZO2, K.KABASHIMA2, W.P.TAN1, S.H.TAN1
National Skin Centre1, Singapore Immunology Network and Skin Research Institute of Singapore2
Basal cell carcinoma (BCC), the most ubiquitous skin cancer world-wide, has a wide range of clinicopathological subtypes. The histological morphologies are closely related to the aggressiveness and prognostic outcome, with infiltrative or morphoeic BCC being more locally aggressive and associated with higher tumour recurrence after surgery. Our study explores the role of Asporin (ASPN), a small leucine-rich repeat proteoglycan, in the stromal infiltration of BCC.
We first performed experimental studies exploring the role of ASPN in the proliferation and migration of keratinocytes by using in vitro cell proliferation and wound healing assays respectively. Protein expression was analysed by using immunohistochemistry (IHC) to compare the immunohistochemical staining pattern of ASPN among 24 BCC samples, comprising of nodular (n=11), infiltrative (n=11) and mixed nodular-infiltrative (n=2) BCCs.
In the keratinocyte proliferation study, cell counts in the ASPN 1000ng/ml group were 2 times higher than the control group (p=0.02). In the keratinocyte migration study, the decrease in wound width in our scratch assays had a mean of 196μm in the ASPN group compared to 64.3μm the control group (p=0.002).
In the IHC analysis, nodular and infiltrative BCC subtypes showed that ASPN expression in infiltrative BCC is extensively expressed in the stroma and in the immediate peritumoral/stroma as compared to a more cellular pattern in nodular BCC.
Our study demonstrate that ASPN promotes cell proliferation and cell migration in BCC. Furthermore, the ASPN protein expression is demonstrated in the tumour-stromal environment and is distinct from the cellular expression in nodular BCC.