Abstract
IntroductionLaminin332 (α3; ß3; γ2 chains) has been identified as an important macromolecule in cancer invasion and metastasis, influencing cell differentiation, migration, adhesion, cell proliferation and survival.The α3, β3, and γ2 chains of LAM-332 are encoded by three distinct genes, LAMA3, LAMB3, and LAMC2, respectively. LAMC2 is associated to the invasive and metastatic abilities of several tumour types such as colon and pancreas. However, the molecular role of LAMC2 in cervical carcinomas has not yet been fully elucidated.We investigated the functional significance of LAMC2 in cervical carcinomas: squamous cell carcinomas (SCC) and adenocarcinoma (ADC) as well as its role in SCC of the cervix.Material and methodsSiHa (SCC) and HeLa (ADC) cell lines were used. The expression of LAMA3, LAMB3, LAMC2 and EGFR was evaluated by qPCR in the presence/absence of EGF. Lamγ2 levels were evaluated by immunofluorescense. Lamγ2 role in migration and invasion was evaluated by wound healing and trans-well assays in control, EGF stimulated and LAMC2 silenced cells (shRNA). Immunohistochemical study evaluated lamα3, β3, and γ2 chains and EGFR, in formalin-fixed, paraffin-embedded in 122 cases, both in situ (n=15) and invasive cervical carcinomas: SCC (n=106) and ADC (n=41). Fisher’s exact test was performed for statistical analysis.Results and discussionsEGF stimulates the migration and invasion in SiHa cells. However knocking-down Lamγ2 decreases cell migration and invasion capacities in SiHa cells. Also, the knockdown of LAMC2 lead to an increased transcription of LAMA3 and LAMB3 genes only in SiHa. The immunohistochemical study demonstrated that lamγ2 chain in SCC cases was significantly associated with invasion (p=0.0001) and with that histological type (p=0.0183). In SCC cases, there was also a significant association of lamß3 and γ2 chains overexpression (p=0.008). Lamα3 was associate with ADC type (p<0.0001). EGFR immuno-overexpression was also associated with SCC (p<0.0001).ConclusionLaminin332 and EGFR are differently expressed in the two most common histological types of cervical carcinomas (SCC and ADC). Lamγ2 expression is associated with SCC in both in vitro and clinical context and Lamg2 -dependent invasion is probably mediated by EGFR dependent signalling pathways.Together, results demonstrate a role of extracellular matrix proteins in the progression of cervix carcinoma. Additionally, Siha and HeLa can be an effective in-vitro models for an overview of the processes involved in cervical cancer progression.
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