Poster Presentation 28th Lorne Cancer Conference 2016

Primary and regionally metastatic melanomas contain high proportions of cells with tumorigenic and metastatic potential (#144)

Clare G Fedele 1 2 3 , Samantha Boyle 1 , Leon di Stefano 4 , Ismael Vergara 4 , Lachlan McIntosh 4 , Vincent Corbin 4 , Tony Papenfuss 1 4 , Mark Shackleton 1 3
  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  2. Pathology, University of Melbourne, Melbourne, Australia
  3. Sir Peter MacCallum Dept Oncology, University of Melbourne, Melbourne, Australia
  4. Walter and Eliza Hall Institute, Parkville, Victoria, Australia

More so than most other cancers, primary cutaneous melanomas are notorious for their ability to metastasize despite being very small in size. However, very little is known about the nature of melanoma cells that comprise early stage tumors. For example, it is not known whether cells with tumorigenic potential and with the ability to metastasize are frequent or rare in primary cutaneous melanomas, as these cancers are rarely available for evaluation in patient-derived xenograft (PDX) assays.

Here we show, using highly efficient PDX modeling, that cells with tumorigenic potential are abundant even in good prognosis melanomas. Across nine primary cutaneous melanomas and nine regionally metastatic melanomas transplanted into NSG mice, no significant differences were observed in the frequencies of tumorigenic cells identified empirically in these tumors, or in the growth rates of secondary PDX tumors. Remarkably, an in situ melanoma from one patient was found to contain high proportions of cells with tumorigenic potential. Cells derived from patient metastases were more likely to metastasize in mice compared to cells from primary lesions, however even some good prognosis primaries contained cells with metastatic potential.

To compare primary and metastatic disease directly, single cells isolated from matched primary cutaneous and regionally metastatic melanomas from the same patients were transplanted into NSG mice. All melanomas contained abundant tumorigenic cells (10% - 44%) that formed clonal tumors with similar average growth rates and similar propensities to metastasize. Evaluation of clonal tumor genotypes suggested that cells in primary melanomas possess a similar, if not greater, potential than cells in metastases for generating intra-tumoral heterogeneity.

These data indicate that tumorigenic and metastatic potential are present in high proportions of cells in primary cutaneous melanomas, which are biologically similar to regionally metastatic disease.