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Xiao, Jerry; Sharma, Utsav; Arab, Abolfazl; Miglani, Sohit; Bhalla, Sonakshi; Suguru, Shravanthy; Suter, Robert; Mukherji, Reetu; Lippman, Marc E; Pohlmann, Paula R; Zeck, Jay C; Marshall, John L; Weinberg, Benjamin A; He, Aiwu Ruth; Noel, Marcus S; Schlegel, Richard; Goodarzi, Hani; Agarwal, Seema
Cancers, 03/2023, Volume: 15, Issue: 6Journal Article
Circulating tumor cells (CTCs), a population of cancer cells that represent the seeds of metastatic nodules, are a promising model system for studying metastasis. However, the expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here we report the development of a combined CTC and cultured CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers. The propagated CTCs yielded a highly aggressive population of cells that could be used to routinely and robustly establish primary tumors and metastatic lesions in CDXs. Differential gene analysis of the resultant CTC models emphasized a role for NF-κB, EMT, and TGFβ signaling as pan-cancer signaling pathways involved in metastasis. Furthermore, metastatic CTCs were identified through a prospective five-gene signature ( , , , , and ). Whole-exome sequencing of CDX models and metastases further identified mutations in constitutive photomorphogenesis protein 1 ( ) as a potential driver of metastasis. These findings illustrate the utility of the combined patient-derived CTC model and provide a glimpse of the promise of CTCs in identifying drivers of cancer metastasis.
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