thumb|Representative phase-contrast image of LNCaP cells. Scale bars represent 100 μm.

thumb|Properties of common PCa cell lines

LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells.

One major obstacle to conducting the most clinically relevant prostate cancer (PCa) research has been the lack of cell lines that closely mimic human disease progression. Although the generation of AI cell lines has been quite successful as demonstrated in the “classic” cell lines DU145 and PC3, the behavior of these cells in bone does not fully mimic clinical human disease. It is well established that human PCa bone metastasis form osteoblastic lesions rather than osteolytic lesions seen in other cancers like breast cancer. Similarly, PC-3 and DU145 cells form osteolytic tumors. To develop an AI-PCa cell model that more closely mimics clinical disease, LNCaP sublines have been generated to provide the most clinically relevant tissue culture tools to date.

History

The LNCaP (Lymph Node Carcinoma of the Prostate) cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 × 10<sup>5</sup> cells/sq cm; doubling time, 60 hr), form clones and are highly resistant to human fibroblast interferon.

]] -->

Wu et al. (1994) reproduced the human-derived LNCaP tumors in immunocompromised mice by co-injection of LNCaP cells with MS human bone fibroblasts. Cells were subcutaneously injected at multiple sites into the mouse flank and after approximately 4 weeks of growth, tumors were easily detectable by physical examination and had a high rate of growth (17-33 mm3/day).

When cultured in a “promineralization medium” that contains ascorbic acid (known to promote skeletal-like ECM formation in osteoblasts) and a source of phosphate (for hydroxyapatite formation), C4-2B cells produce and retain approximately 8x more mineralized calcium than parental LNCaP cells. C4-2B cells also express higher levels of osteoprotegerin (OPG), alkaline phosphatase, bone sialoprotein (BSP), Osteocalcin (OCN), RANKL, and Osteonectin (OSN) mRNA, all of which are highly expressed by osteoblasts.

Osteoblast promoter activity is also higher in C4-2B cells when compared to LNCaP, as indicated by Cbfa1 transcription factor expression. Concomitantly, BMP7, a known inducer of Cbfa1, is also more highly expressed in C4-2B cells, further suggesting many osteoblast-like properties. LN95 cells differ from parental LNCaP cells morphologically, with pronounced dendritic extensions, and molecularly, with Androgen receptor variant expression similar to that of AR-V7<sup>High</sup> VCaP cells. Notably, LN95 cells are significantly more tumour initiating than their parental counterparts in vivo. While LNCaP-AI are wholly androgen independent, they retain high expression of Androgen receptor, low expression of AR-V7, and remain androgen responsive.

References

Further reading

  • Transfection data on LNCaP Cells
  • Cellosaurus entry for LNCaP
  • Cellosaurus entry for C4
  • Cellosaurus entry for C4-2
  • Cellosaurus entry for C4-2B
  • Cellosaurus entry for C5