Data_Sheet_1_HPV DNA Associates With Breast Cancer Malignancy and It Is Transferred to Breast Cancer Stromal Cells by Extracellular Vesicles.docx

A causal link between Human Papillomavirus (HPV) and breast cancer (BC) remains controversial. In spite of this, the observation that HPV DNA is over-represented in the Triple Negative (TN) BC has been reported. Here we remark the high prevalence of HPV DNA (44.4%) in aggressive BC subtypes (TN and HER2+) in a population of 273 Italian women and we convey the presence of HPV DNA in the epithelial and stromal compartments by in situ hybridization. As previously reported, we also found that serum derived-extracellular vesicles (EVs) from BC affected patients contain HPV DNA. Interestingly, in one TNBC patient, the same HPV DNA type was detected in the serum-derived EVs, cervical and BC tissue samples. Then, we report that HPV DNA can be transferred by EVs to recipient BC stromal cells that show an activated phenotype (e.g., CD44, IL6 expression) and an enhanced capability to sustain mammospheres (MS) formation. These data suggest that HPV DNA vehiculated by EVs is a potential trigger for BC niche aggressiveness.

人乳头瘤病毒（Human Papillomavirus, HPV）与乳腺癌（Breast Cancer, BC）之间的因果关联仍存在争议。尽管如此，已有研究报道三阴性乳腺癌（Triple Negative Breast Cancer, TN BC）组织中人乳头瘤病毒DNA的检出率偏高。本研究在273名意大利女性队列中，发现侵袭性乳腺癌亚型（三阴性乳腺癌与HER2阳性乳腺癌）中人乳头瘤病毒DNA的高检出率达44.4%；同时通过原位杂交（in situ hybridization）技术证实，人乳头瘤病毒DNA存在于上皮与间质细胞组分中。如既往研究所述，我们同样发现乳腺癌患者血清来源的细胞外囊泡（Extracellular Vesicles, EVs）中携带有乳腺癌相关人乳头瘤病毒DNA。值得注意的是，在1名三阴性乳腺癌患者的血清来源细胞外囊泡、宫颈组织及乳腺癌组织样本中，均检测到了同一型别的人乳头瘤病毒DNA。本研究进一步证实，细胞外囊泡可将人乳头瘤病毒DNA递送至受体乳腺癌间质细胞，使后者呈现激活表型（如CD44、IL6表达上调），并增强其维持乳腺球（Mammospheres, MS）形成的能力。上述结果提示，经细胞外囊泡转运的人乳头瘤病毒DNA，可能是驱动乳腺癌微环境侵袭性增强的潜在诱因。