Effects of colonization by Fusobacterium nucleatum on breast cancer growth and progression
Fusobacterium nucleatum is a commensal bacterium of the oral cavity and other mucosal sites. It is found in the same districts in pathogenic conditions too so it can be ascribed to the opportunistic pathogens category as well. Normally, F. nucleatum in the oral cavity contributes to the constitution of oral biofilms with the other members of oral microbiota. The same bacteria are the drivers of inflammation causing periodontitis. With regards to extra-oral diseases, preterm birth and adverse events during pregnancy are the better explained effects of F. nucleatum colonization.
In addition to this, it has been demonstrated that F. nucleatum has a primary role in driving the progression of colorectal cancer and in reducing the activity of intratumoral immune cells. Indeed, high levels of F. nucleatum colonization in tumoral tissues are positively correlated with a poor prognosis.
In their work, Lishay Parhi et Al., described the colonization of human breast cancer by the same bacterium and its dynamic. The group showed that F. nucleatum manages to attach to tumour cells by expressing lectin Fap-2 that allows the binding to Gal-GalNAc, a highly expressed molecule in malignant breast cancer. Normal tissues do not show so abundant Gal-GalNAc expression as well as F. nucleatum presence. Experiments using Fap2-deficient K50 F. nucleatum mutants showed a strong impairment in the attachment to tumour cells.
Additional evidence showed that during the transition from benign hyperplasia to carcinoma in situ a sharp rise in Gal-GalNAc expression occurs. The recognition of the latter molecule allows F. nucleatum colonization through lectin Fap-2. Indeed, in normal tissues, that do not show Gal-GalNAc expression, F. nucleatum is not detectable. Conversely, signals from these bacteria are high in tissues that display a large abundance of Gal-GalNAc that are tumoural ones. Probably, bacteria reach the tumoural site through blood circulation from the mouth.
Additional observations highlighted that F. nucleatum not only colonizes the tumour microenvironment but contributes to the enlargement of the tumour size. Antibiotic treatment is efficient in preventing this enlargement but does not reduce the tumoural mass size.
The ways in which F. nucleatum contributes to the expansion of the tumour are multiple. The results showed that the inoculation with the bacterium resulted in lower levels of CD4 and CD8 positive T cells and in a reduced abundance of the tumour microenvironment infiltrating immune cells as well. The bacterium may induce apoptosis in lymphocytes through lectin Fap2. Moreover, MMP-9, a metalloproteinase involved in cancer pathology and progression, was overexpressed. This impaired expression may be driven by F. nucleatum.
Eventually, these evidences state that F. nucleatum, that has already been demonstrated having a primary role in the colonization and expansion of colorectal cancer, is able to colonize breast cancer and promote its progression, expansion and metastasis. All in all, this knowledge could be exploited to develop alternative therapeutic approaches that specifically target this bacterial population and allow an interruption of further tumour enlargement.