Isolation and Molecular Characterization of Circulating Melanoma Cells

Xi Luo; Devarati Mitra; Ryan J. Sullivan; Ben S. Wittner; Anya M. Kimura; Shiwei Pan; Mai P. Hoang; Brian W. Brannigan; Donald P. Lawrence; Keith T. Flaherty; Lecia V. Sequist; Martin McMahon; Marcus W. Bosenberg; Shannon L. Stott; David T. Ting; Sridhar Ramaswamy; Mehmet Toner; David E. Fisher; Shyamala Maheswaran; Daniel A. Haber

doi:10.1016/j.celrep.2014.03.039

Isolation and Molecular Characterization of Circulating Melanoma Cells

Xi Luo, Devarati Mitra, Ryan J. Sullivan, Ben S. Wittner, Anya M. Kimura, Shiwei Pan, Mai P. Hoang, Brian W. Brannigan, Donald P. Lawrence, Keith T. Flaherty, Lecia V. Sequist, Martin McMahon, Marcus W. Bosenberg, Shannon L. Stott, David T. Ting, Sridhar Ramaswamy, Mehmet Toner, David E. Fisher, Shyamala Maheswaran, Daniel A. Haber

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

Abstract

Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

Original language	English (US)
Pages (from-to)	645-653
Number of pages	9
Journal	Cell Reports
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2014.03.039
State	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2014.03.039

Cite this

Luo, X., Mitra, D., Sullivan, R. J., Wittner, B. S., Kimura, A. M., Pan, S., Hoang, M. P., Brannigan, B. W., Lawrence, D. P., Flaherty, K. T., Sequist, L. V., McMahon, M., Bosenberg, M. W., Stott, S. L., Ting, D. T., Ramaswamy, S., Toner, M., Fisher, D. E., Maheswaran, S., & Haber, D. A. (2014). Isolation and Molecular Characterization of Circulating Melanoma Cells. Cell Reports, 7(3), 645-653. https://doi.org/10.1016/j.celrep.2014.03.039

Luo, X, Mitra, D, Sullivan, RJ, Wittner, BS, Kimura, AM, Pan, S, Hoang, MP, Brannigan, BW, Lawrence, DP, Flaherty, KT, Sequist, LV, McMahon, M, Bosenberg, MW, Stott, SL, Ting, DT, Ramaswamy, S, Toner, M, Fisher, DE, Maheswaran, S & Haber, DA 2014, 'Isolation and Molecular Characterization of Circulating Melanoma Cells', Cell Reports, vol. 7, no. 3, pp. 645-653. https://doi.org/10.1016/j.celrep.2014.03.039

@article{050969953d4e48549e957305fe962c90,

title = "Isolation and Molecular Characterization of Circulating Melanoma Cells",

abstract = "Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.",

author = "Xi Luo and Devarati Mitra and Sullivan, {Ryan J.} and Wittner, {Ben S.} and Kimura, {Anya M.} and Shiwei Pan and Hoang, {Mai P.} and Brannigan, {Brian W.} and Lawrence, {Donald P.} and Flaherty, {Keith T.} and Sequist, {Lecia V.} and Martin McMahon and Bosenberg, {Marcus W.} and Stott, {Shannon L.} and Ting, {David T.} and Sridhar Ramaswamy and Mehmet Toner and Fisher, {David E.} and Shyamala Maheswaran and Haber, {Daniel A.}",

note = "Funding Information: The authors thank C. Hart, A. McGovern, C. Koris, and the Massachusetts General Hospital clinical research coordinators for help with clinical studies; L. Libby for mouse studies; F. Ozsolak and P. Milos (Helicos) for RNA-seq; and J. Walsh, J. Lennerz, and M. Ulman for microscopy expertise. This work was supported by grants from Stand Up To Cancer (D.A.H., M.T., and S.M.), the Howard Hughes Medical Institute (D.A.H.), the Melanoma Research Foundation (X.L.), the National Foundation for Cancer Research (D.A.H.), and the NIH (NIH CA129933 to D.A.H. and NIBIB EB008047 to D.A.H. and M.T.). Massachusetts General Hospital has filed for patent protection for CTC technology. ",

year = "2014",

doi = "10.1016/j.celrep.2014.03.039",

language = "English (US)",

volume = "7",

pages = "645--653",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Isolation and Molecular Characterization of Circulating Melanoma Cells

AU - Luo, Xi

AU - Mitra, Devarati

AU - Sullivan, Ryan J.

AU - Wittner, Ben S.

AU - Kimura, Anya M.

AU - Pan, Shiwei

AU - Hoang, Mai P.

AU - Brannigan, Brian W.

AU - Lawrence, Donald P.

AU - Flaherty, Keith T.

AU - Sequist, Lecia V.

AU - McMahon, Martin

AU - Bosenberg, Marcus W.

AU - Stott, Shannon L.

AU - Ting, David T.

AU - Ramaswamy, Sridhar

AU - Toner, Mehmet

AU - Fisher, David E.

AU - Maheswaran, Shyamala

AU - Haber, Daniel A.

N1 - Funding Information: The authors thank C. Hart, A. McGovern, C. Koris, and the Massachusetts General Hospital clinical research coordinators for help with clinical studies; L. Libby for mouse studies; F. Ozsolak and P. Milos (Helicos) for RNA-seq; and J. Walsh, J. Lennerz, and M. Ulman for microscopy expertise. This work was supported by grants from Stand Up To Cancer (D.A.H., M.T., and S.M.), the Howard Hughes Medical Institute (D.A.H.), the Melanoma Research Foundation (X.L.), the National Foundation for Cancer Research (D.A.H.), and the NIH (NIH CA129933 to D.A.H. and NIBIB EB008047 to D.A.H. and M.T.). Massachusetts General Hospital has filed for patent protection for CTC technology.

PY - 2014

Y1 - 2014

N2 - Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

AB - Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

UR - http://www.scopus.com/inward/record.url?scp=84899974076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899974076&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2014.03.039

DO - 10.1016/j.celrep.2014.03.039

M3 - Article

C2 - 24746818

AN - SCOPUS:84899974076

SN - 2211-1247

VL - 7

SP - 645

EP - 653

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

Isolation and Molecular Characterization of Circulating Melanoma Cells

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this