CeCa-5 cell line characterization
This study reports the successful isolation and long-term cultivation of non-immortalized HPV-negative cervical cancer cells. The isolated primary cells were observed to be highly proliferative, HPV-negative, and derived from cervical squamous cell carcinoma. The expression of relevant cancer-associated antigens was investigated on the primary cancer tissue and the isolated cells using immunohistochemistry and flow cytometry. A combination of karyotyping, fluorescence in situ hybridization, optical genome mapping, and next-generation sequencing was used for in-depth characterization of primary cervical cancer cells. The genetic profiling showed a monosomy 13 and a duplication of chromosome 3q, concomitant with pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, or DNA damage repair, such as MLH1, RB1, PIK3CA, and TP53. Comparative sequencing of genomic DNA from blood, cervical smear, and the tumor cell line provided insights into the sequence of early and late mutational events. Live-cell imaging and flow cytometry were used to examine targeted treatment strategies based on potential genetic vulnerabilities of the primary cells. Treatment with common anti-cancer drugs revealed a high sensitivity to olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. Thus, the HPV-negative primary tumor cell line described here, named CeCa-5, represents a valuable new model to study cervical cancer and to develop targeted therapies for this understudied subgroup.
This study reports the successful isolation and long-term cultivation of non-immortalized HPV-negative cervical cancer cells. The isolated primary cells were observed to be highly proliferative, HPV-negative, and derived from cervical squamous cell carcinoma. The expression of relevant cancer-associated antigens was investigated on the primary cancer tissue and the isolated cells using immunohistochemistry and flow cytometry. A combination of karyotyping, fluorescence in situ hybridization, optical genome mapping, and next-generation sequencing was used for in-depth characterization of primary cervical cancer cells. The genetic profiling showed a monosomy 13 and a duplication of chromosome 3q, concomitant with pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, or DNA damage repair, such as MLH1, RB1, PIK3CA, and TP53. Comparative sequencing of genomic DNA from blood, cervical smear, and the tumor cell line provided insights into the sequence of early and late mutational events. Live-cell imaging and flow cytometry were used to examine targeted treatment strategies based on potential genetic vulnerabilities of the primary cells. Treatment with common anti-cancer drugs revealed a high sensitivity to olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. Thus, the HPV-negative primary tumor cell line described here, named CeCa-5, represents a valuable new model to study cervical cancer and to develop targeted therapies for this understudied subgroup.
Hannover Medical School